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.

Significant Microorganisms

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

Bakterie	Produkce	Princip	Forma
E. coli	β-lactamase (penicillinase)	decomposition of penicillin	obtained
		fluoroquinolone efflux
		ribosome modification
Haemophilus spp.	β-lactamase	rozklad penicilinu	obtained
Klebsiela spp.	carbapenemase	inaktivace β-laktamů
		ampicilin rezistentní	primary
N. gonorhoeae	β-lactamase	decomposition of penicillin	obtained
N. meningitis	β-lactamase	decomposition of penicillin	obtained
Pseudomonas spp.		beta-lactam efflux	primary
Salmonella spp.	"Salmonela Genomic Island"	various resistances
Stafylocccus spp.	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

Links

Related Articles

• Antibiotika
• Antibiotika (neonatologie)
• MRSA a VRSA

External Links

• • Rational antibiotic therapy - interactive algorithm + test

References

• JULÁK, Jaroslav. Introduction to medical bacteriology. 1st edition. Prague: Karolinum, 2006.  ISBN 8024612704 .

• BRHELOVÁ, Eva. Beta-lactamases with a broad spectrum of action, their genetic basis and detection methods [online] . Brno, 2010, also available from < https://is.muni.cz/th/uyohp/text_bakalarky.pdf?so=nx >. Bachelor thesis

• VOTAVA, Miroslav, et al. Medical microbiology special. 1st edition. Brno: Neptun, 2003. 495 pp.  ISBN 80-902896-6-5 .