Clostridioides Difficile

Research project
Active research
Project owner
Institute of Biomedicine

Short description

Infectious Medicine is constantly facing new challenges. Gunnar Jacobsson's research team is taking a broad approach to meet pragmatic clinical infection issues. Sepsis- and bacteremia epidemiology are our fundamental project areas in time of antibiotic resistance and pandemics. In addition, we want to find the balance point in clinically effective antibiotic use that simultaneously takes into account resistance threats. Health-related infections, such as Clostrioides Difficile, threaten clinical infectious achievements and are central to our work.

Severe sepsis and bacteraemia  

Sepsis is a common healthcare problem. Worldwide, as many as 33 million people are affected annually, and case fatality rates are high. Due to methodologic challenges, data on the incidence of sepsis have been difficult to compile. Owing to differences in sepsis criteria and methodologies used, as well as in the populations studied, the incidences reported have varied by a factor of more than one hundred. While chart-based prospective population studies are considered Gold standard, they are often difficult to perform, especially on large populations.

Our group has published work on the epidemiology of severe sepsis in western Sweden and is elaborating aspects of prognosis of severe sepsis in present projects. We are also collaborating within an international network, IBSC – International Bacteraemia Surveillance Collaborative, to report and analyse trends in bacteraemia in different parts of the world.

Prudent antibiotic use and antibiotic resistance

Antibiotic resistance is a global problem with important medical and economic implications. The more antibiotics used, the more likely development of resistant microorganisms. Antibiotics and other medicines are often prescribed too easily for a number of reasons, including the desire to have a good relationship with patients, the belief that patients expect to receive medications, time pressure and inadequate policies or guidelines ignorance among practitioners regarding the conditions leading to resistance and the way the healthcare system works. It may be less convenient for the physician to wait and see how an illness develops and whether there is need for antibiotics than to simply write a prescription right away.

Conservation, decreasing the use of antibiotics through different means, slows down the development of resistance and provides more time to develop alternatives. Even if antibiotic resistance is a global problem, its solutions happen at the national and regional levels. Education of healthcare providers, and the public on correct antibiotic use and problems with antibiotic resistance is a central form of conservation. Educational strategies include meetings with didactic lectures and distribution of informational leaflets.

A Cochrane review reports improved antibiotic use in five of six studies with dissemination of educational materials in printed form or meetings; the median effect size based on the type of study ranged from about 11 to 43 percent. However, the effect of educational activities is often found to be transient and should be combined with active interventions. Use of rapid diagnostic tests such as the concentration of C-reactive protein as a point-of-care test, and rapid antigen detection test for group A streptococci, and academic detailing, or face-to-face education, have been found to have a positive effect on appropriate prescribing of antibiotics compared with personnel meetings and educational materials.  

The level of antibiotic prescription is low in Sweden compared with many other European countries. However, there are differences in rates of prescriptions between different regions and municipalities. Hedin et al compared municipalities in Sweden with high and low antibiotic prescription rates and found that neither socioeconomic factors nor differences in infection symptoms or number of physician consultations could explain these differences. They concluded that reasons for these prescription rate differences are unclear, but they might be due to differences in prescribing behavior of physicians.  

Our group collaborate with various researchers in many fields; primary care, economics, political science, to examine obstacles for prudent use of antibiotics at national and regional level, in primary care and in the hospital setting.  

Surveillance, transmission and prevention of Clostrioides difficile infections in healthcare

Clostridioides difficile (formerly known as Clostridium difficile) (CD) is a sporulating gram-positive bacteria causing opportunistic gastrointestinal infection, Clostridioides difficile Infection (CDI).  Aggressive strains of CD, such as ribotype 027 and 078, pose a serious threat with increasing global incidence. With increased toxin production, as well as acquired resistance to antibiotics, they are adapted to transmission within healthcare facilities in a similar fashion as other multi-drug resistant organism. The ability to sporulate adds an extra dimension, as the spores can endure most environmental challenges, including commonly used disinfectants. Severe outbreaks with multiple deaths occur regularly, including in Sweden. CD-induced diarrhoea also facilitates the transmission of other multi-drug resistant organisms that may be present in the intestinal microbiota, such as enterobacteriaceae with extended spectrum betalactamases or carbapenemases.  There are still unsolved questions regarding the sources of CDI, especially since sporulation allows for transmission over long distances in both time and space. The relative contribution of community-acquired spores, transmission from symptomatic as well as asymptomatic patients, and transmission via healthcare workers and inanimate objects within hospitals largely remains to be investigated. In the Nordic countries specifically, there is an apparent paradox with relatively high CDI incidence despite a prudent antibiotic consumption and a generally high standard of infection control measures. However, one of the most important risk factors for CDI is use of broad-spectrum antibiotics.  The pathogen was considered one of five urgent antibiotic resistance threats in the US by the CDC in 2019. The majority of CDI are healthcare-facility associated (HCF-CDI). It is one of the most common healthcare associated infections, in the US even the most frequent. Recurrent CDI (rCDI) is common (20-35 percent) and causes significant costs for healthcare and great suffering for the patients. Risk factors for rCDI, others than infection control and prevention-related outlined above, are not fully known but age, use of PPI, further antibiotic use, renal failure, treatment with fluoroquinolones are often mentioned.

We have in our recently published study shown that antibiotic stewardship aiming to minimize cephalosporin use led to a reduction in incidence of HCF-CDI with more than 50 procent (Karp 2019). At Södra Älvsborgs Sjukhus, SÄS, an Antibiotic Stewardship Program that lowered the cephalosporin use with 87 percent was implemented in 2008. At the similar hospital Skaraborgs Sjukhus, SkaS, the cephalosporin use was high during this period. Preliminary data from this data collection also suggests that cephalosporine use might be an independent risk factor for rCDI but the first data sample was too small to show statistical significance. We have proposed a method for surveillance of possible outbreaks, based on historic ward-specific incidence numbers, which is currently in use at two hospitals in Region Västra Götaland, and the first aim (surveillance) is to test the validity of this method against a thorough mapping of C. difficile transmission within hospitals. We will try to find all symptomatic healthcare-associated C. difficile transmissions within the catchment areas of two hospitals (Södra Älvsborgs Sjukhus and Skaraborgs Sjukhus) (population: approximately 600 000) over two years. The second aim (transmission) is to examine to what extent the hospital environment is a probable source for transmission. Our third aim (prevention) is to investigate if cephalosporin use, both individual use and at an aggregated level (hospital), prior to initial HCF-CDI (iCDI) is an independent risk factor to develop rCDI. If the hypothesis is true, the prevention of rCDI could be achieved by cephalosporin reduction (as we have already shown for iCDI).

Gunnar Jacobsson

Principal Investigator

Group members

Lars Ljungström

Johan Karp

Jon Edman