Resistance of clinically important bacteria to ATB

Bacterial resistance to commonly used antibiotics is a growing problem in the treatment of bacterial infections. Some organisms have primary resistance due to the simple properties of the bacterium (eg natural production of beta-lactamases). The agent develops secondary resistance during antibiotic therapy. Different types of bacteria apply different mechanisms, the most common of which include:


 * production of penicillinase and other beta-lactamases,
 * change in PBP (penicillin-binding proteins),
 * active efflux.

Staphylococci
The drug of choice for staphylococci was previously penicillin (discovered due to its effects on S. aureus ). Over time, the strains acquired the ability to produce the enzyme penicillinase by transferring plasmids (blaZ gene). This beta-lactamase hydrolytically degrades the beta-lactam ring of penicillins. A similar mechanism of resistance applies to other beta-lactam ATBs. Today, 80-90% of S. aureus strains are resistant to penicillin. In resistant strains, beta-lactamase inhibitors are used together with the active substance, penicillinase-resistant penicillins and glycopeptide antibiotics (egvancomycin ). Vancomycin-resistant strains are also emerging due to the thick layer of peptidoglycan (VISA). In 2002, the first VRSA strain ( S. aureus completely resistant to vancomycin) was isolated by obtaining the van A gene from enterococci.

Streptococci
In streptococci, penicillin is the drug of choice.

Steptococcus pyogenes
Complications can arise from mixed infections where beta-lactamase-producing strains are present. Erythromycin, clindamycin , lincosamides, tetracyclines are used. However, agents of community infections may be resistant to these macrolides ( S. pyogenes MLSR ).

Streptococcus pneumoniae
Penicillin-resistant strains transfer genetic information by plasmid conjugation or bacteriophage transduction. In the Czech Republic, about 10% of strains are resistant. Resistance arises due to a change in the structure of PBP (penicillin-binding proteins), so these bacteria do not produce beta-lactamase. Intravenous administration of high doses of penicillin, amoxicillin, cephalosporins and erythromycin is effective. Polyresistant strains (DRSP) also appear.

Viridizing Streptococcus
Increasingly, they are resistant to penicillin, other beta-lactams, cephalosporins and erythromycin, cefotaxime, vancomycin are used.

Haemophilus spp.
Ampicillin and amoxycillin are recommended for the treatment of hemophilia, but more strains producing beta- lactamase are used - in this case we use cephalosporins, chloramphenicol, cotrimoxazole.

Neisseria gonorrhoeae
Formerly well sensitive to penicillin, today strains producing penicillin - an alternative therapy is ofloxacin, azithromycin.

Neisseria meningitidis
Therapy for meningococcal infections is based on large doses of penicillin iv or im. Therapeutics producing penicillinase use chloramphenicol, cotrimoxazole, and cephalosporins.

Klebsiella spp.
Klebsiells are primarily resistant to ampicillin, hospital strains show multidrug resistance. They produce carbapenemases that inactivate many beta-lactam ATBs and inhibit cephalosporins, penicillins, carbapenems. The causative agents of nosocomial infections are among EBSL organisms.

Escherichia coli
Beta -lactam therapy, fluoroquinolones, aminoglycosides are used for extraintestinal E.coli infections. Some strains show resistance to beta-lactams because they produce beta-lactamases based on the transmission of genetic information by the plasmid. Today, 60% of cases are resistant to aminopenicillins, 15% to cephalosporins. They are resistant to fluoroquinolones by the mechanism of efflux (active depletion of ATB from the cell by membrane pumps) or by altering target structures (enzymes responsible for bacterial DNA replication). In the Czech Republic, resistance to fluoroquinolones in 25% of cases. Resistance to aminoglycosides arises from the modification of ribosomes (methylation, adenylation), which become biologically inert to aminoglycoside ATBs. In our country, 10% of cases are resistant to aminoglycosides.

Salmonella spp.
Salmonella are resistant due to point mutation or gene transfer (R-plasmid). We are currently defining the so-called Salmonella Genomic Island, which is a block of 43 genes encoding resistance to ATB (ampicillin, chloramphenicol, streptomycin, sulfonamides, tetracycline).

Pseudomonas spp.
Pseudomonads are naturally resistant to penicillins and beta-lactams by efflux. Pseudomonas aeruginosa is used as a causative agent of nosocomial infections and is usually multi-resistant.

Overview of Mechanisms
{| class="wikitable" !Bakterie!!Produkce!!Princip!!Forma ! rowspan="3" |E. coli ! rowspan="2" |Klebsiela spp.
 * β-lactamase (penicillinase)||decomposition of penicillin
 * obtained
 * ||fluoroquinolone efflux
 * ||ribosome modification
 * Haemophilus spp.||β-lactamase
 * rozklad penicilinu||obtained
 * ||ribosome modification
 * Haemophilus spp.||β-lactamase
 * rozklad penicilinu||obtained
 * Haemophilus spp.||β-lactamase
 * rozklad penicilinu||obtained
 * carbapenemase
 * inaktivace β-laktamů||
 * ||ampicilin rezistentní||
 * N. gonorhoeae ||β-lactamase
 * decomposition of penicillin
 * obtained
 * N. meningitis ||β-lactamase
 * decomposition of penicillin
 * obtained
 * Pseudomonas spp.|| ||beta-lactam efflux
 * decomposition of penicillin
 * obtained
 * Pseudomonas spp.|| ||beta-lactam efflux
 * Pseudomonas spp.|| ||beta-lactam efflux

! rowspan="2" |Stafylocccus spp.
 * Salmonella spp.||"Salmonela Genomic Island"||various resistances
 * Salmonella spp.||"Salmonela Genomic Island"||various resistances
 * β-lactamase
 * decomposition of penicillin
 * obtained
 * thick layer of peptidoglycan
 * prevents the penetration of vancomycin
 * obtained
 * Streptococcus spp.|| ||penicillin resistance
 * Streptococcus pneumoniae||modified PBP
 * penicillin resistance
 * obtained
 * }
 * Streptococcus pneumoniae||modified PBP
 * penicillin resistance
 * obtained
 * }

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