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Anti-infection: How to Treat Resistant Enterococci

Anti-infection: How to Treat Resistant Enterococci. The antibiotic sensitivity spectrum of enterococci is very annoying. They are inherently resistant to β-lactam antibiotics.

1 Introduction

The WHO treats Vancomycin-resistant Enterococcus (VRE) as a pathogen with a higher priority. It is important to identify enterococci with multi-drug resistant bacteria (MDR).

Enterococcus faecalis and Enterococcus faecium can cause infections in critically ill patients, and their antibiotic sensitivity is complex.

2. Inherent resistance to resistance mechanisms

The antibiotic sensitivity spectrum of enterococci is very annoying. They are inherently resistant to β-lactam antibiotics. Enterococcus can express a specific binding protein (pbp5), which is distributed on the outer membrane of the cell, and it has a low binding capacity to β-lactam antibiotics, which results in poor efficacy of these antibiotics.

At the same time, enterococci have a natural moderate degree of resistance to aminoglycosides. This is because enterococci have poor cell membrane permeability and can prevent macromolecular antibiotics from entering the bacteria. In addition, enterococci are highly resistant to cephalosporins and clindamycin. Except for the newly developed new generation of cephalosporins (ceftaroline which is active against Enterococcus faecalis), others are almost inactive against enterococci; even ampicillin-sensitive enterococci, combined with cephalosporins for treatment, are all There is no synergy.

Among the enterococci isolated in Europe, 30% are highly resistant to aminoglycoside antibiotics (HLAR strain). This resistance can be achieved by modifying ribosomes or producing aminoglycoside modifying enzymes. Moderate drug resistance can be treated with a combination of β-lactam (which destroys cell membranes) and aminoglycosides, but it is not always effective for the HLAR strain.

3. Vancomycin with acquired resistance

In Europe and the United States, VanA operon resistance is an important resistance mechanism of VRE (the proportion of VRE can reach 15%). VanA operon can affect the expression of vanZ gene, which can cause vancomycin and teicoplanin resistance .

Most epidemic strains in Australia are of the VanB operator type, and these pathogens lack the vanZ gene. Prolonged hospital stay, ICU treatment, chronic renal insufficiency and dialysis, abdominal surgery, invasive procedures, vancomycin use, meropenem use, fluoroquinolone use, and ceftriaxone use military VRE. Hand hygiene is an important means to block cross-infection of VRE. The resistance mechanisms between enterococci can spread to each other, leading to a wide range of drug resistance among bacterial populations.

VRE strains of pathogenic bacteria can persist in the human body for months or even years, causing repeated infections. The proportion of recurrent infections in patients without immunosuppression can reach 10%, and the proportion of secondary infections in patients with immunodeficiency can reach as high as 35%. For VRE and HLAR strains, there are few treatments available, and the treatment options that can be selected are: daptomycin, linezolid, and tigecycline.

4. Acquired resistance to daptomycin

Enterococcus can achieve resistance to daptomycin in many ways, such as changing the site of action of daptomycin in Enterococcus faecalis, and the electrostatic repulsion of the cell membrane of Enterococcus faecium. Daptomycin-resistant enterococci are different in different regions, and the overall proportion is not high (1%). Low concentrations of daptomycin (6 mg/kg) may induce resistance to enterococci. High concentrations of daptomycin (10-12 mg/kg) may reduce the resistance of enterococci.

Daptomycin combined with β-lactam drugs can play a synergistic effect, thereby reducing the resistance of enterococci to daptomycin. In vitro experiments have confirmed that the best synergistic effect is ceftaroline.

Other combined use programs are still under study, such as combined fosfomycin, tigecycline and so on.

5. Acquired resistance to linezolid

Enterococcus can achieve resistance to linezolid by changing its target. The degree of 23S gene alteration is proportional to the degree of MIC increase. The proportion of linezolid-resistant strains is not high, <1%. Preferential use of linezolid and β-lactam drugs, hematology ward treatment, etc. are considered risk factors for linezolid resistance. Linezolid is still a powerful treatment for enterococcal bloodstream infections (BSI), even if the pathogen is resistant to daptomycin. Oxazolidinone antibiotics do not seem to have a synergistic effect with other antibiotics and do not need to be used in combination.

6. Acquired resistance to tigecycline

Tigecycline-resistant enterococci have been isolated, but the proportion is not high, less than 0.5%. Tigecycline is an optional treatment for MDR enterococcal infection, but it should be considered as a salvage treatment and it is not recommended to use it first. For critically ill patients and patients with gram-negative bacteria infections in the ICU, high-concentration use of tigecycline (100 mg, twice a day) can have a good effect, but for enterococcal infections, relevant research data Very rare.

7. Treatment options for abdominal infection

In community-acquired abdominal infections, empirical treatment often does not cover enterococci, unless the patient has a high risk factor for MDR. It is generally recommended to cover enterococci in the treatment plan when treating post-operative infections or hospital-acquired infections.

Patients with immunosuppression, severe infection, high risk of MDR, and endocarditis need to be treated with enterococcal infection. Ampicillin-sensitive enterococci can be treated with penicillin; if ampicillin is resistant, vancomycin and teicoplanin can be selected. For VRE, daptomycin and linezolid can be selected.

When other drugs are clinically unavailable, you can choose to use tigecycline. Liver function needs to be closely monitored during medication. For abdominal infection, the control of the source of infection is the most basic.

8. Treatment options for bloodstream infections

Enterococcus faecium bloodstream infection is the most common of enterococcal bloodstream infections. The treatment of bloodstream infections first needs to identify the source of infection, and then actively deal with the source of infection, such as removing the relevant catheter. The first choice for the treatment of VRE bloodstream infection is linezolid and daptomycin.

The meta-analysis showed that the fatality rate of daptomycin (6 mg/kg) in the treatment of VRE bloodstream infection 30 was higher than that of linezolid; but another study showed that daptomycin (> 8-10 mg/kg) was effective Better than linezolid. This suggests that when using daptomycin, you need to pay attention to the dosage. Comparing the therapeutic effects of high-dose daptomycin, conventional-dose daptomycin and linezolid, it was found that the results of high-dose daptomycin and linezolid were similar, and both were superior to low-dose daptomycin.

If the daptomycin MIC is 3-4 mg/L, then the probability of treatment failure with daptomycin will increase. These cases should be treated with linezolid.

9. Infective endocarditis of treatment options

The first choice for the treatment of infective endocarditis is a bactericide, usually beta lactam combined with aminoglycoside drugs to treat endocarditis caused by enterococci.

The first-line treatment is: ampicillin combined with gentamicin or vancomycin combined with gentamicin, but renal function needs to be paid attention to during treatment. Studies have shown that ampicillin combined with ceftriaxone treatment for infective endocarditis caused by HLAR strain is safe, and the treatment success rate can reach 75%, making this option a treatment option for patients with renal insufficiency, thereby avoiding amino The use of glycoside drugs.

High-dose daptomycin (10-12 mg/kg) is an option for the treatment of infective endocarditis, but it needs to be used in combination with β-lactam drugs. In the treatment of infective endocarditis, linezolid should be avoided unless there are no other alternatives.

10. Summary

VRE and MDR infections caused by enterococci have serious consequences and should be paid close attention to in clinical practice. For enterococcal infection, the source of infection must be controlled first. Ampicillin sensitive strains should be treated with penicillin first.

For infections of different parts, high-dose daptomycin, linezolid, and tigecycline can be selected for salvage treatment. The effect of combination medication is better than single-agent therapy. For these patients, infection risk assessment and rapid diagnosis are required so that the clinic can take appropriate treatment plans in time.