Page 99 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART I Basic Bacteriology
88
The term high-level resistance refers to resistance that
cannot be overcome by increasing the dose of the antibi-
drugs as well, for simplicity, only the most characteristic
drugs are listed. Some strains of the bacteria listed in
otic. A different antibiotic, usually from another class of
Table 11–2 are highly resistant to multiple antibiotics,
drugs, is used. Resistance mediated by enzymes such as
β-lactamases often result in high-level resistance, as all the
namely methicillin-resistant S. aureus (MRSA; see
drug is destroyed. Low-level resistance refers to resistance
(VRE; see Chapter 15), multidrug-resistant Streptococcus
that can be overcome by increasing the dose of the antibi-
otic. Resistance mediated by mutations in the gene encod-
pneumoniae (MDR-SP; see Chapter 15), P. aeruginosa (see
ing a drug target is often low level, as the altered target can Chapter 15), vancomycin-resistant Enterococcus faecium
Chapter 18), and multidrug-resistant Mycobacterium
still bind some of the drug but with reduced strength.
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tuberculosis (MDR-MTB; see Chapter 21).
To illustrate the use of these terms, strains of Neisseria
gonorrhoeae that produce penicillinase cannot be treated
successfully with penicillin G. They exhibit high-level resis-
tance, and a different drug such as ceftriaxone must be used.
Chromosome-Mediated Resistance
However, strains of N. gonorrhoeae that synthesize altered
penicillin-binding proteins exhibit low-level resistance and
Chromosomal resistance is due to a mutation in the gene
can be treated successfully with high-dose penicillin G.
that codes for either the target of the drug or the transport
Hospital-acquired infections are significantly more likely
system in the membrane that controls the uptake of the
to be caused by antibiotic-resistant organisms than are
community-acquired infections. This is especially true for
–9
–7
ranges from 10 to 10 , which is much lower than the
hospital infections caused by Staphylococcus aureus and enteric
frequency of acquisition of resistance plasmids. Therefore,
gram-negative rods such as Escherichia coli and Pseudomonas drug. The frequency of spontaneous mutations usually
chromosomal resistance is less of a clinical problem than is
aeruginosa. Antibiotic-resistant organisms are common in the
plasmid-mediated resistance.
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hospital setting because widespread antibiotic use in hospitals
The treatment of certain infections with two or more
selects for these organisms. Furthermore, hospital strains are
drugs is based on the following principle. If the frequency
often resistant to multiple antibiotics. This resistance is usually
due to the acquisition of plasmids carrying several genes that
–7
A is 10 (1 in 10 million) and the frequency that the same
encode the enzymes that mediate resistance.
bacterium mutates to become resistant to antibiotic B
Table 11–2 describes certain medically important
–8
is 10 (1 in 100 million), then the chance that the bacte-
bacteria and the main drugs to which they are resistant.
rium will become resistant to both antibiotics (assuming
that the antibiotics act by different mechanisms) is the
–15
product of the two probabilities, or 10 . It is therefore
TABLE 11–2 Medically Important Bacteria That
Exhibit Significant Drug Resistance
both antibiotics. Stated another way, although an organism
may be resistant to one antibiotic, it is likely that it will be
Type of Bacteria Clinically Significant Drug highly unlikely that the bacterium will become resistant to
Resistance
effectively treated by the other antibiotic.
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Gram-positive cocci
Staphylococcus aureus
Penicillin G, methicillin/nafcillin
Plasmid-Mediated Resistance
Streptococcus pneumoniae
Penicillin G
Enterococcus faecalis, E. faecium
-vancomycin
clinical point of view for three reasons:

Gram-negative cocci
(1) It occurs in many different species, especially gram-
Penicillin G
Neisseria gonorrhoeae
negative rods.
Gram-positive rods

(2) Plasmids frequently mediate resistance to multiple

None
drugs.
Gram-negative rods
(3) Plasmids have a high rate of transfer from one cell to
Haemophilus influenzae
β-Lactams, aminoglycosides
Pseudomonas aeruginosa
Resistance plasmids (resistance factors, R factors) are
Enterobacteriaceae 2 3 Ampicillin 1 1 another, usually by conjugation.
β-Lactams, aminoglycosides
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extrachromosomal, circular, double-stranded DNA mole-
Mycobacteria

cules that carry the genes for a variety of enzymes that can
Isoniazid, rifampin
Mycobacterium tuberculosis
degrade antibiotics and modify membrane transport sys-
Isoniazid, rifampin, and many others
M. avium-intracellulare
1
β-Lactams are penicillins and cephalosporins.
tant mechanisms of resistance for several important drugs.
2
The family Enterobacteriaceae includes bacteria such as Escherichia coli, Enterobac-
R factors may carry one antibiotic resistance gene or may
ter cloacae, Klebsiella pneumoniae, and Serratia marcescens.
carry two or more of these genes. The medical implications
3
Some strains of M. tuberculosis are resistant to more than two drugs.
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