Aer

AER is the acronym for vancomycin-resistant enterococci. Vancomycin-resistant enterococci are primarily recruited from the increasing reservoir of E. faecium isolates. They are usually resistant to all glycopeptides; to this extent, they are also referred to as glycopeptide-resistant enterococci or GRE. E. gallinarum and E. casseliflavus have intrinsic vancomycin resistance. They are only slightly virulent and are generally not classified as nosocomial AER.

Enterococci are considered to be "opportunistic infectious agents", which only cause infection under certain conditions. For example, AER infections mainly affect multimorbid patients, most of whom have undergone extensive pre-treatment with antibiotics, typically patients after organ transplantation, haematological-oncological patients, dialysis patients and patients who have been in intensive care for a long time. Common infections are bloodstream infections, catheter-associated infections and intra-abdominal infections. In most cases, AER colonisation precedes invasive infection (McDermott H et al. 2018; Chen H et al. 2013). A variety of other antibiotic resistance factors limit the treatment options for AER infections. They are therefore a dreaded nosocomial problem germ.

A distinction is made between two types of resistance:

• Van-A (resistance to vancomycin and teicoplanin) and
• Van-B (resistance to vancomycin, in vitro sensitivity to teicoplanin).

Glycopeptide resistance in enterococci is encoded in the so-called van genes. These are gene clusters that each code for several proteins. So far, a total of 9 different van gene clusters are known. Some of them are species-specific, either plasmid- or genome-coded and also differ in their vancomycin or teicoplanin resistance.

Vancomycin and teicoplanin have a bactericidal effect by attaching themselves to the free C-terminal end of the peptide side chain of the bacteria, thus preventing the enzymatic cross-linking of the peptidoglycan. This reduces the osmotic resistance of the bacterium and leads to cell lysis. Vancomycin-resistant enterococci, however, succeed in making the binding of glycopeptide antibiotics more difficult by altering the target structure. This modification reduces the affinity of vancomycin to the target structure by a factor of 1,000.

Currently the vancomycin resistance rate of Enterococcus faecium in Germany is about 10% and is slightly declining. In the Benelux countries it is 1% in Greece and Spain 30%.

In principle, it is possible to prepare an antibiogram by means of an agar diffusion test for enterococci. However, especially a questionable vancomycin resistance should better be clarified by a microdilution test, because this way the minimum inhibition concentration can be determined.

In 2010, the following minimum inhibitor concentrations were defined by EUCAST as limits for glycopeptide resistance in enterococci.

• Vancomycin: sensitive ≤ 4 mg/l; resistant > 4 mg/l
• Teicoplanin: sensitive ≤ 2 mg/l; resistant > 2 mg/l

AERs are generally difficult to deal with. Carrier status alone is not an indication for therapy and antibiotic treatment is difficult to control. It is also unclear whether invasive AER infection leads to increased mortality. The corresponding data situation is contradictory (DiazGranados CA et al. 2005; Cho SY et al. 2013). In general, however, enterococci are pathogens with only low pathogenicity compared to Staphylococcus aureus or most Gram-negative bacteria. In order to be clinically significant, a severe underlying disease must usually already be present, which is crucial for the prognosis of the patient.

Screening programmes: Increasingly, screening programmes for high-risk patients are being introduced, which, for example, prescribe stool testing for AER on admission and, if positive, require appropriate hygiene measures. Since colonisation rates of around 10% have been described in such high-risk populations (e.g. haematological-oncological patients), these measures have enormous nursing and financial implications. The benefits are controversial (Huang SS et al. 2013). In addition, there are negative psychological effects and the stigmatisation of AER patients should not be underestimated.

If, as is often the case, AER is also resistant to ampicillin, linezolid is the drug of choice. The slightly older quinupristin-dalfopristin does not offer any advantage. It is not effective against E. faecalis. Conversely, daptomycin is more effective against E. faecalis and only less effective against E. faecium. The combination of daptomycin with tigecycline in endocarditis with a linezolin-resistant AER is described.

Tetracyclines, erythromycin and fluoroquinolones are more frequently considered after an antibiogram, as is cotrimoxazole. The latter should not be used in enterococcal infections (Huggett S et al. 2018).

AERs can permanently survive not only in the intestines, but also on the skin and hands of patients (and medical staff) and in the patient's environment. They can therefore be easily transmitted from patient to patient in risk areas. This risk is particularly high in patients with diarrhoea. In this respect, meticulous basic hygiene is of eminent importance.

In Europe, farm animals, as well as non-hospitalised, healthy people, represent a significant reservoir for AER. This can be explained by the massive use of Avoparcin in animal fattening. The use of Avoparcin in animal fattening is prohibited in the European Union. In this respect, the prevalence rates of AER are also decreasing.

1. Chen H et al (2013) Linezolid-resistant clinical isolates of enterococci and Staphylococcus cohnii from a multicentre study in China: molecular epidemiology and resistance mechanisms. Int J Antimicrob agents 42: 317-321
2. Cho SY et al (2013) Impact of vancomycin resistance on mortality in neutropenic patients with enterococcal bloodstream infection: a retrospective study. BMC Infect Dis 13: 504
3. DiazGranados CA et al (2005) Comparison of mortality associated with vancomycin-resistant and vancomycin-susceptible enterococcal bloodstream infections: a meta-analysis. Clin Infect Dis 2005; 41: 327-333
4. Huang SS et al (2013)Targeted versus universal decolonization to prevent ICU infection. N Engl J Med 368: 2255-2265
5. Huggett S et al (2018) Antibiotics Primer 2018/2019 Asclepius, Medical Scientific Publishing Company. p.51-52AER leaflet(Download)
6. McDermott H et al (2018) Vancomycin-Resistant Enterococci (AER) in The Intensive Care Unit in a Nonoutbreak Setting: Identification of Poten-tial Reservoirs and Epidemiological Associations Between Patient and Environmental AER. Infect Control Hosp Epidemiol 39: 40-45
7. Rosko AE et al (2014) Vancomycin-resistant enterococci infection: not just for the transplanted. Leuk Lymphoma 55: 1320-3125