Bacterial resistance to Antibiotics represents a major public health problem.
The epidemiology of enteric bacteria is changing rapidly due to global spread of a resistance mechanism called extended spectrum beta-lactamase (ESBL), responsible for resistance to almost all penicillins and cephalosporins.
In the early 1980s, soon after the clinical introduction of third generation cephalosporins, resistant strains of bacteria have first been described. These were strains of Klebsiella pneumoniae , carrying a resistance plasmid able to hydrolyze all beta-lactam antibiotics except for cephamycins and carbapenems ( 1 ). Until the early 2000s several enzymes were described (TEM , SHV , CTX- M) that could be isolated from bacteria colonizing or infecting hospitalized patients especially in intensive care units ( 2).
But since 2000, this resistance mechanism spread very rapidly among Enterobacteria and especially in the population outside hospitals and predominantly in Escherichia coli. Within 10 years, this commensal digestive tract bacterium (10 10 germs E.Coli/gram of feces) became the most affected species to ESBL type resistance. The responsible enzyme often is a cefotaximase (CTX -M) (3). Resistance is acquired by plasmid transmission from non-pathogenic environmental bacteria (Kluyvera) that are natural carriers of this resistance mechanism, followed by transmission between Enterobacteria. In France the proportion of resistant strains to C3G among strains causing bacteremia has increased from 1 to 6% in E. coli between 2001 and 2008 and from 5 to 17 % in K. pneumoniae between 2005 and 2008. In 2008 the estimated number of ESBL-E.coli bacteraemia in France is approximately 2000 cases and for K. pneumoniae bacteremia 1000 cases.( 4 )
ESBL Enterobacteria are also resistant to other antibiotics, because of the presence of genes in the same plasmids or chromosomal mutations. In 2008, a french study conducted in public health institutions - Hôpitaux de Paris showed that 58% of strains were resistant to gentamicin, 43% to amikacin and 68% to ciprofloxacin (5). These strains are described all around the world, also affecting people with no particular risk factor (6). In 2006 in Israel, 13.7 % of community bacteremia was due to ESBL bacteria (7). An over 40% increase of these resistant strains is currently documented in Greece, India and North African countries.
In Nice data from the University-Hospital and medical laboratories in the city show 4-12 % of ESBL E.coli in urine samples. Our region is particularly exposed because of tourism and its opening to the south.
Microbiological diagnosis is difficult due to heterogeneity of beta- lactamases and frequent changes in the recommended criteria of detection procedures. As far as detection is concerned automated antibiogram systems are reliable but biologists must perform a confirmatory test. Some methods proposed by the "CLSI (Clinical and Laboratory Standards Institute)" and the "Committee of antibiogram of the French Society for Microbiology" allow sensitivity and specificity close to 100%: Etest , disk or combined synergy test (4)
The infections involved are mainly urinary tract infections and can be severe in case of renal or prostatic affection or bacteremia. Recent studies show an inadequate treatment in 40-60 % due to resistance, and consequently an increased morbidity mortality rate (8,9). Standard treatment of severe infection consists of carbapenems. However, the significant worldwide increase of antibiotic use leads to emergence of new resistance mechanisms, the carbapenemases, which mainly affect strains of Klebsiella pneumoniae in the Mediterranean countries (Greece, Turkey, Israel ..) or the Indian subcontinent ( NDM- 1). The absence of efficient antibiotic treatment of these resistant bacteria results in an increase of the mortality rate.
Some risk factors for ESBL infection were clearly identified:
· Antibiotic treatment with 3rd generation cephalosporins or fluoroquinolones 6 months prior to infection
· old age
· female gender
· co-morbidities such as diabetes, kidney failure, dialysis , recurrent urinary tract infections and gynecological surgery (10).
· Travels in endemic area
Family members of an infected person have 25 % of transmission risk (11). Many studies show the presence of ESBL Enterobacteria in all types of animals (livestock, pets and wild) as well as in food products. These bacteria are also present in hospital sewage, sewage purification plants and even drinking water (Nepal) (4).
Dissemination of ESBL Enterobacteria is the result of two phenomena:
1. The selection pressure by antibiotics and their overuse in human or veterinary medicine
2. Cross - transmission of the bacterium or its genes.
After transmission either from human to human or through environmental factors, resistant Enterobacteria strains are settling in the digestive flora. Risk of spread is linked to the reservoir size. A person, symptomatic or asymptomatic, with ESBL-infection can pollute the environment with as much as 10 10 E.coli excrement elimination daily. This explains the new name given to this endemo-epidemic: "new fecal peril "( 4 ).
Controlling the risk of spread of these bacteria is a major issue. In hospitals, the recommendations proven effective, particularly in MRSA infections, are based on hygiene measures as washing hands, screening, isolation and decolonization. The difficulty in ESBL is rather based on the reservoir size which is inaccessible to decolonization, the difficulty to detect potential carriers, the rapid spread of the phenomenon and the high costs of contact-isolation measures. A recent study aimed to analyze the effectiveness of measures to limit transmission in hospitals, pointed out that there is no prospective trial on the subject ( 12). In rehabilitation centers or nursing homes it is difficult to maintain such hygienic contact precautions since maintaining a personalized environment is a priority. There is also a lack of data on evolution and transmission of strains within these institutions (13). Concerning the situation at home there is no literature-data available on how or if hygiene precautions for multi-resistant bacteria carriers are being applied.
In this context, the French High Council of Public Health has published recommendations in February 2010, emphasizing the need to disseminate information on this issue to all health care actors involved(4).
In the PACA East region there already exists a network of collaboration between the university hospital CHU and other general hospitals, destined to homogenize and standardize diagnostic and therapeutic practices in infectious diseases . We opened this network to community health care partners including medical analysis laboratories, private clinics, medical practitioners to organize the fight against the spread of ESBL-bacteria . Together we have designed and approved a tool to treat colonized or infected patients called "ESBL Tool-Kit". We also established an alert system after ESBL detection for rapid diagnostic transmission and rapid initiation of appropriate treatment. Early 2012 most network partners were ready to apply this tool.