A global study of hospitalized patients found that more than a third of inpatients with cirrhosis had multidrug-resistant (MDR) bacterial infections, and almost 10% had extensively drug-resistant (XDR) infections. Furthermore, the prevalence of MDR infections varied widely by country, from 16% in the U.S. to 73% in India, where the XDR infection rate was 33%.
“Differences in the prevalence of MDR bacterial infections in different global regions indicate the need for different empirical antibiotic strategies in different regions of the world,” wrote Paolo Angeli, MD, PhD, of the University of Padua in Italy, and colleagues.
In the study, online in Gastroenterology, the team also stressed the need to redouble efforts to reduce the spread of MDR bacteria in this at-risk patient population, explaining that while the risk of dying from some complications of liver cirrhosis has progressively decreased in the U.S., the risk from bacterial sepsis has risen.
Unexpectedly, the study found that the use of prophylaxis with quinolone antibiotics against spontaneous bacterial peritonitis (SBP) was not a predictor of MDR infections. This finding contrasts with most previous research, in which quinolone prophylaxis is a main driver of MDR infections in cirrhosis, Angeli and co-authors noted.
The investigators, members of the International Club of Ascites Global Study Group, collected data on 1,302 hospitalized patients with cirrhosis and bacterial or fungal infections at 46 centers (15 in Asia, 15 in Europe, 11 in South America, and five in North America), from October 2015 through September 2016. The cohort, with a mean age of 57, included 565 individuals (43%) from Europe, 416 (32%) from Asia, and 321 (25%) from the Americas; 69% of the patients were male.
Alcohol was the most common cause of cirrhosis, followed by hepatitis C virus and nonalcoholic steatohepatitis. As expected, hepatitis B virus infection was more common in Asia. Patients had advanced liver disease, with a high prevalence of ascites (77%) and hepatic encephalopathy (38%). The mean model of end stage liver disease (MELD) score was 21±8, the MELD sodium score (MELD-Na) was 24±8, and the Child-Turcotte-Pugh (CTP) score was 10±2. Notably, 35% of patients had acute-on-chronic liver failure at diagnosis of infection.
Patients were followed until death, liver transplantation, or discharge. The global prevalence of MDR bacteria was a disturbing 34% (95% confidence interval 31-37), a figure higher than that in previous studies, Angeli and colleagues explained. The greatest prevalence emerged in Asia, at 51% overall, while the prevalence in Canada and parts of Europe was 20-30%.
Overall, about 50% of infections were community-acquired, followed by healthcare-associated and nosocomial infections at 26%. The most common infections were as follows:
- SBP (27%)
- Urinary tract infections (UTIs, 22%)
- Pneumonia (19%)
In addition, a greater prevalence of pneumonia and UTIs and a lower prevalence of SBP were found in Asia than in the Americas and Europe. At diagnosis, 14% of patients already had septic shock.
The 34% prevalence should be a wake-up call, Scott L. Friedman, MD of Icahn School of Medicine at Mount Sinai in New York City, who was not involved in the research, told MedPage Today. “This is a unique and comprehensive study that is unlikely to be replicated with this kind of rigor any time soon. It’s a warning that antibiotics have to be used judiciously and that the possibility of MDR should always be a consideration, particularly in those regions where it is more likely.”
Antibiotic selection should be guided by identification of the bacteria, Friedman added. He noted that while there is a high level of vigilance in the U.S., where standard care is based on microbial identification, vigilance should be maintained and heightened in patients with cirrhosis since they are at greater risk of infection and are already immunocompromised.
Among independent risk factors for MDR infections were infection in Asia, use of antibiotics in the 3 months before hospitalization, previous healthcare exposure, and having an invasive procedure in the previous month, the study showed. In addition, MDR infections were more common in young patients, in males, and in those with worse liver function according to MELD-Na and CTP scores.
The notable differences in the distribution and type of MDR bacteria across geographic indicate that standardized antibiotic treatment schemes can’t be applied worldwide, Angeli and co-authors warned. “These schemes need to be adapted to national, regional, or even local microbiological epidemiology.”
The team recommended widespread use of rapid antimicrobial susceptibility tests in order to speed up or de-escalate the administration of appropriate antibiotic treatment.
Study limitations, the researchers said, included the lack of participating centers from Africa and other geographic areas. In addition, tools for the detection of specific genetic resistance were not available.
The study was supported by the Italian Ministry of Education, University, and Research.
Angeli and co-authors reported having no conflicts of interest.
Friedman reported having no competing interests in relation to his comments.