Index
A
absolute clinical resistance, 157
Absorption, Distribution, Metabolism, Excretion, Toxicity (ADMET) properties, 144–145
accuracy of surveillance, denominator effect and, 126–127
Acinetobacter baumannii, 11
acquired resistance, 12
acyclovir, 49
adamantane resistance, 173–174
adamantane-resistant avian flu virus H5N1, 173
adamantanes, 168
addiction modules, 94–95
adenosine triphosphate (ATP), 219
ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) properties, 144–145
adverse effects of antibiotics, 200–201
agricultural practice
removal of fluoroquinolones from U.S. poultry use, 133–134
surveillance in, 135
AIDS, 25
airborne infections
avoiding, 178–182
disease transmission, 114
aminoglycosides, 37
ancient malaria remedies, 44
The Andromeda Strain (Crichton), 114
anthrax outbreak of 2001, 176
antibacterials, 6. See also antibiotics
antibacterial classes and resistance mechanisms, 37–40
generalized effects of, 40–41
antibiotic resistance, definition of, 8
adamantanes, 168
adverse effects of, 200–201
antibacterials
antibacterial classes and resistance mechanisms, 37–40
generalized effects of, 40–41
antibiotic classes and resistance mechanisms, 34–36
antifungal classes and resistance mechanisms, 41–43
antihelminth classes and resistance mechanisms, 45
antiprotozoan classes and resistance mechanisms, 43–44
antiviral classes and resistance mechanisms, 45–46
broad-spectrum antibiotics, 7, 32
choosing optimal antibiotics, 197–199
discovering new antibiotics, 12, 31–34
computer-assisted drug design, 144–145
consideration of resistance during drug discovery, 163–164
drug safety and side effects, 145–146
economic problems, 146
high-throughput screening, 143–144
model systems for drug research, 140–141
natural sources of antibiotics, 141–142
new antibiotics as temporary solutions, 139
dosages
antibiotic concentrations above MPC, 159–160
combination therapy, 162–163
combining MPC with PK/PD targets, 160–161
dosing to eradicate susceptible cells, 158–159
evolution of antibiotic classes, 50–52
lethal compounds, 32
measuring static and lethal action of, 20–21
molecular mechanism of antibiotic action, 32
neuraminidase inhibitors, 168–169
overuse of, 14
restricting use of
agricultural use, 155
consideration of resistance during drug discovery, 163–164
environmental contamination by antibiotics, 155–157
human consumption, 150–154
and risk for subsequent resistance, 200
specialized (narrow-spectrum) antibiotics, 32
static compounds, 31
antifungal classes and resistance mechanisms, 41–43
antihelminth classes and resistance mechanisms, 45
antimalaria drugs, 43
antimicrobial streamlining, 106
antimutant strategies for antibiotic development, 164
antiprotozoan classes and resistance mechanisms, 43–44
antituberculosis agents, 52
antiviral classes and resistance mechanisms, 45–46
ANZCOSS, 59
artesunate, 187
arthropod-borne infections
avoiding, 186–187
disease transmission, 118–120
malaria, 223
ancient malaria remedies, 44
antibiotic-resistant malaria, 118–119
antimalaria drugs, 43
disease transmission, 118–119
risk in travelers, 186–187
-ase suffix, 208
Asian Flu pandemic (1957-1958), 170
Aspergillus fumigatus, 21, 157
atoms, 207–208
ATP (adenosine triphosphate), 219
Australian Society for Antimicrobials, 59
autoclaves, 181
avian flu H5N1, 171–174
avoiding resistant pathogens
airborne infections, 178–182
arthropod-borne infections, 186–187
clashes between personal and public health, 177–179
food-borne diseases
disease risks from food-borne pathogens, 188–189
E. coli, 190–194
Salmonella, 190–195
MRSA, 182–184
overview, 177
sexually transmitted infections, 185
avoparcin, 136
azidothymidine (AZT), 47
azithromycin, 38
azoles, 157
AZT (azidothymidine), 47
B
Bacillus anthracis, 140
antibacterials, 6. See also antibiotics
antibacterial classes and resistance mechanisms, 37–40
generalized effects of, 40–41
biofilms, 29
Borrelia, 120
Campylobacter, 133–134, 189, 194–196
cellular structure of, 221
Clostridium difficile, 87–88
culturing, 19–20
defined, 17
digestive-tract pathogens, 115–116
direct-contact pathogens, 116
Enterococcus, 136
explained, 4
focus on populations, 28–29
Gram-negative, 18
Gram-positive, 18
humans as ecosystems for bacteria, 56
Klebsiella pneumoniae, 121–122
Mycobacterium tuberculosis
completely drug-resistant tuberculosis (CDR-TB), 111
determining antibiotic resistance by genotyping, 130–131
disease transmission, 108–113
extensively resistant (XDR) tuberculosis, 111–113
in HIV-positive persons, 111
in homeless populations, 113
latent tuberculosis, 110
multi-drug resistant (MDR), 111–112
testing for exposure to, 109
treatment of, 110–111
vaccination against, 109
persister cells, 28
Plasmodium falciparum, 118
Plasmodium knowlesi, 118
Plasmodium malariae, 118
Plasmodium ovale, 118
Plasmodium vivax, 118
Pseudomonas aeruginosa, 80
quorum sensing, 28
reproduction, 221
ribosomes, 37
rickettsia, 119–120
S. aureus, 74
SOS response, 79
Streptomyces, 142
bacterial pneumonia, 175
bacteriophages, 96–97
Bacteroides, 38
Bacteroidetes, 7
Baquero, Fernando, 14
ß-lactamase, 81
biofilms, 29
bleach, 53
blood-borne pathogens, 121
Borrelia, 120
bovine spongiform encephalitis (mad cow disease), 26
broad-spectrum antibiotics, 7, 32
buds (yeast), 222
C
CA-MRSA (community-associated MRSA), 2, 117, 182
Campylobacter, 133–134, 189, 194–196
Candida albicans, 5, 18, 41, 154, 222
carbapenemase, 122
carbohydrates, 218–219
Carson, Rachel, 187
cassette integration, 92
CC398, 184
CDC (Centers for Disease Control), 14
CDR-TB (completely drug-resistant tuberculosis), 111
Centers for Disease Control (CDC), 14, 127
Chagas disease, 44
Chain, Ernst, 34
children, treatment strategies for, 65–66
chinchona tree, medicinal properties for malaria, 44
chloramphenicol, 142
Choleraesuis, 195
choosing optimal antibiotics, 197–199
clarithromycin, 38
clashes between personal and public health, 177–179
clavulanic acid, 81
Clinical and Laboratory Standards Institute (United States), 20
Clinical Laboratory Standards Institute (CLSI), 58
Clostridium difficile, 38, 87–88
CLSI (Clinical Laboratory Standards Institute), 58
codons, 210
cold viruses, 114
combination therapy, 162–163
combining MPC with PK/PD targets, 160–161
commensals, 5
community-associated MRSA (CA-MRSA), 2, 117, 182
completely drug-resistant tuberculosis (CDR-TB), 111
complex-17, 136
Compound 606 (salvorsan), 33
computer-assisted drug design, 144–145
contaminated food
disease risks from food-borne pathogens, 188–189
E. coli, 190–194
Salmonella, 190–195
correlation between human consumption of antibiotics and resistance, 150
counting pathogens, 18–23
covalent bonds, 207
Crichton, Michael, 114
Cryptosporidium, 44
culturing bacteria, 19–20
cytochrome P-450 (CYP450) enzyme system, 65
cytokines, 7
D
daptomycin, 39
DDT, 187
DEET, 186
definition of antibiotic resistance, 8
Denmark
ban of use of antibiotics as growth promotors, 155
MRSA initiatives, 205
surveillance in food animals, 135
denominator effect and surveillance accuracy, 126–127
deoxyribonucleic acid. See DNA
detecting viral antibiotic resistance, 174–175
development of new antibiotics, 12
digestive-tract pathogens, 115–116
digitalis, 142
dihydropteroate synthetase, 39
direct-contact pathogens, 116
directly observed therapy (DOT), 110
disc diffusion, 57–58
discovering new antibiotics
computer-assisted drug design, 144–145
consideration of resistance during drug discovery, 163–164
drug safety and side effects, 145–146
economic problems, 146
high-throughput screening, 143–144
model systems for drug research, 140–141
natural sources of antibiotics, 141–142
new antibiotics as temporary solutions, 139
disease outbreak response. See surveillance
disease transmission. See transmission of resistant disease
disseminated resistance, 12
diversity of pathogens, 5, 17–18
explained, 209–213
genomic islands, 102–103
horizontal gene transfer, 8
integrons, 101–102
nucleic acid probes, 23–24
recombination, 92–93
replication, 38
resistance mutations, 157
effect on pathogen fitness, 86
explained, 74–75
fluoroquinolone-resistant gyrase mutants, 82
induced mutations, 79–80
mutant selection window hypothesis, 77–79
mutator mutations and increased mutation frequency, 83
stepwise selection of resistance, 75–76
topoisomerases, 38
transposons, 99
Domagk, Gerhard, 31–34
dosing strategies, 15. See also treatment strategies
antibiotic concentrations above MPC, 159–160
changing dosage levels, 204
combination therapy, 162–163
combining MPC with PK/PD targets, 160–161
determining with PK/PD (pharmacokinetics/ pharmacodynamics) indices, 62–65
dosing to eradicate susceptible cells, 158–159
DOT (directly observed therapy), 110
drinking water, antibiotic contamination of, 156
drug discovery
computer-assisted drug design, 144–145
consideration of resistance during, 163–164
drug safety and side effects, 145–146
economic problems, 146
high-throughput screening, 143–144
model systems for drug research, 140–141
natural sources of antibiotics, 141–142
new antibiotics as temporary solutions, 139
“druggable” proteins, 145
Duesberg, Peter, 25
duration of treatments, 67
dynamic nature of DNA molecules, 212
E
E-test, 57
echinofungins, 42
economic problems with antibiotic discovery, 146
educating about dangers of antibiotic overuse, 203
efflux pumps, 80
Ehrlich, Paul, 31–33
electron microscopy, 18
electrons, 207
EMEA (European Medicines Evaluation Agency), 58
emergence of resistance
antiseptic and disinfectant use, 84
explained, 73
in individual patients, 73–74, 196–197
molecular mechanisms, 80–82
mutations
effect on pathogen fitness, 86
explained, 74–75
fluoroquinolone-resistant gyrase mutants, 82
induced mutations, 79–80
mutant selection window hypothesis, 77–79
mutator mutations and increased mutation frequency, 83
phenotypic resistance, 84
stepwise selection of resistance, 75–76
treatment time and, 82–83
unintended damage arising from treatment, 87–88
viral resistance, 84–86
empiric therapy, 55–56
Enterococcus, 115
Enterococcus faecalis, 102
global spread of, 136
vancomycin-resistant Entercococcus faecium, 115
environmental contamination by antibiotics, 155–157, 204
enzymes, 208
ergosterol, 41
ESBLs (extended-spectrum ß-lactamases), 81, 122
estradiol, 223
ethambutol, 110
EUCAST (European Committee for Antimicrobial Susceptibility Testing), 20, 58
eukaryotic organisms, 221
European Committee for Antimicrobial Susceptibility Testing (EUCAST), 20, 58–59
European Medicines Evaluation Agency (EMEA), 58
evolution
antibiotic resistance as consequence of, 8
of antibiotic classes, 50–52
extended-spectrum ß-lactamases (ESBLs), 81, 122
extensively resistant (XDR) tuberculosis, 111–113
F
face masks, 180
Falkow, Stanley, 27
Fermicutes, 7
FFP-2 face mask, 180
Fleming, Alexander, 31–33
flexibility of DNA molecules, 212
Florey, Howard, 33
fluconazole, 41
flucytosine, 42
fluoroquinolone-resistant gyrase mutants, 82
evolution of, 50–52
fluoroquinolone resistance, 83
fluoroquinolone-resistant gyrase mutants, 82
removal from U.S. poultry use, 133–135
resistance mechanisms, 38
folate, 40
food-borne disease, avoiding
disease risks from food-borne pathogens, 188–189
E. coli, 190–194
Salmonella, 190–195
formaldehyde, 53
formularies, 68
foscarnet, 46
France, antibiotic use in, 153
frequency of mutations, 28
fungal diseases, 222–223
fungi
cellular structure of, 222
fungal diseases, 222–223
immune modulators and fungal infections, 42
molds, 222
Paracoccidiodes brasiliensis, 223
structure of, 222
yeasts, 222
G
garenoxacin, 52
gatifloxacin, 52
gemifloxacin, 52
general recombination, 92
generalized effects of antibacterials, 40–41
generalized transduction, 98
genes, 210
gene expression, 216
horizontal gene transfer
addiction modules, 95
cassette integration, 92
explained, 91–92
gene mobilization, 99
genomic islands, 102–103
integrons, 101–102
plasmids, 94
recombination, 92–93
relaxase, 103
transformation, 98
genetic recombination, 212
genomic islands, 102–103
genotyping, 130–131
gentamycin, 38
Germany, antibiotic use in, 153
Giardia, 44
glossary, 227–231
glycosomes, 44
Gram, Christian, 18
Gram-negative bacteria, 18
Gram-positive bacteria, 18
griseofulvin, 43
growth promotors, use of antibiotics as, 155
guinea pig test for tuberculosis, 108
gyrase A protein, 82
H
H1N1 influenza, 169–170
H1N2 influenza, 169
H3N2 influenza, 169
H5N1 avian flu, 171–172
HA-MRSA (hospital-associated MRSA), 2–3, 182
hand sanitizers, 199
hantavirus pulmonary syndrome, 182
Hata, Sahachiro, 33
helicases, 212
helminths
diseases caused by, 224
herpes virus, 49–50
high-throughput screening, 143–144
Hill, Bradford, 27
Hippocrates, 142
HIV (human immunodeficiency virus), 25, 46–48, 85–86, 224
homeless populations, tuberculosis and, 113
homologous recombination, 92
Hong Kong Flu pandemic (1968-1969), 170
horizontal gene transfer, 8
cassette integration, 92
explained, 91–92
gene mobilization, 99
genomic islands, 102–103
integrons, 101–102
plasmids
addiction modules, 95
explained, 94
recombination, 92–93
relaxase, 103
transformation, 98
hospital antibiotic policy, 68–69, 106
hospital contact, controlling infections spread by, 123
hospital-associated MRSA (HA-MRSA), 2–3, 182
human consumption of antibiotics
correlation with resistance, 150–152
limiting, 152–154
human immunodeficiency virus (HIV), 25, 46–48, 224
hydrocarbon, 219
hydrophobic interactions, 219
hydroxyl radicals, 41
hyphae, 222
I
identifying clinically resistant pathogens, 9
IDSA (Infectious Disease Society of America), 56
immigrant self-medication, 69–70
immune modulators and fungal infections, 42
immunological tests, 62
individual patients, emergence of resistance in, 73–74, 196–197
induced mutations, 79–80
infection control as local crisis management, 106–107
Infectious Disease Society of America (IDSA), 56
influenza
antiviral resistance to seasonal influenza, 168–170
avian flu H5N1, 171–174
avoiding, 179–180
bacterial pneumonia associated with, 175
membrane protein-2 (M2), 168
pandemic influenza, 170–171
Asian Flu pandemic (1957-1958), 170
H1N1 pandemic (2009), 170
Hong Kong Flu pandemic (1968-1969), 170
public health strategy, 172, 176
Spanish Flu pandemic (1918–1919), 170
quarantine, 179
vaccination against seasonal influenza virus, 167–168
Inner Canon of the Yellow Emperor, 142
integrase inhibitors, 47
integrons, 101–102
interferon-Á release assays, 109
interpretation of surveillance studies, 132
intrinsic resistance, 12
iodine, 53
isolates, 60
K
kanamycin, 38
kinetoplasts, 44
Klebsiella pneumoniae, 11, 121–122
L
LD (lethal dose), 21
lead compounds, 143
leishmaniasis, 44
lethal action of antibiotics, measuring, 20–21
lethal compounds, 32
lethal dose (LD), 21
levamisole, 45
levofloxacin, 50–51
Levy, Stuart, 14
LexA, 79
light microscopy, 18
lincosamides, 38
linezolid, 37
lipids, 219–220
Listeria, 192
local crisis management, infection control as, 106–107
lysogenic bacteriophages, 98
lysogeny, 98
M
M. bovis BCG, 140
M. smegmatis, 140
macrolides, 38
macromolecules, 208
mad cow disease (bovine spongiform encephalitis), 26
malaria, 223
ancient malaria remedies, 44
antibiotic-resistant malaria, 118–119
antimalaria drugs, 43
disease transmission, 118–119
risk in travelers, 186–187
management programs to control hospital antibiotic policy, 68–69
Materia medica, 142
MBC (minimal bactericidal concentration), 21
MDR (multi-drug resistant) tuberculosis, 111–112
measuring
numbers of pathogens, 18–23
static and lethal action of antibiotics, 20–21
mebendazole, 45
membrane protein-2 (M2), 168
metabolic pathways, 220
methicillin, 139
methicillin-resistant Staphylococcus aureus. See MRSA
metronidazole, 44
MexAB-OprM, 80
MexCD-OprJ, 80
MexEF-OprN, 80
MexXY-OprM, 80
MfpA, 83
MIC (minimal inhibitory concentration), 9, 20–21, 55–59, 78, 161
MIC creep, 126
microbes, 4
microbiomes, 7
minimal bactericidal concentration (MBC), 21
minimal effective concentration, 21
minimal inhibitory concentration. See MIC
model systems for drug research, 140–141
molds
Aspergillus fumigatus, 157
cellular structure of, 222
defined, 222
explained, 4
spores, 222
molecular beacons, 129–130
molecular mechanism of antibiotic action, 32
molecular probes, 23–24
molecular resistance mechanisms, 80–82
molecules, 207–208
monkeypox, 26
morphine, 142
mosquitos
transmission of malaria, 118–119
transmission of West Nile Virus, 120
MPC (mutant prevention concentration), 77–78
antibiotic concentrations above MPC, 159–160
combining MPC with PK/PD targets, 160–161
MR2 (membrane protein-2), 168
MRSA (methicillin-resistant Staphylococcus aureus), 1–4
avoiding, 182–184
disease transmission, 117
European MRSA initiatives, 204
susceptibility testing, 60
multi-drug resistant (MDR) tuberculosis, 111–112
multidrug resistant efflux systems, 198
multiple-mode transmission, 121–122
mupirocin, 37
mutant prevention concentration (MPC), 77–78
mutant selection window hypothesis, 77–79
mutants, 8
mutations, 8
effect on pathogen fitness, 86
explained, 74–75
fluoroquinolone-resistant gyrase mutants, 82
frequency of, 28
induced mutations, 79–80
mutant selection window hypothesis, 77–79
mutator mutations and increased mutation frequency, 83
resistant mutants, 157
stepwise selection of resistance, 75–76
mutator mutations and increased mutation frequency, 83
Mycobacterium tuberculosis, 5, 11
antituberculosis agents, 52
antituberculosis program in Peru, 61–62
completely drug-resistant tuberculosis (CDR-TB), 111
determining antibiotic resistance by genotyping, 130–131
disease transmission, 108–113
extensively resistant (XDR) tuberculosis, 111–113
in HIV-positive persons, 111
in homeless populations, 113
latent tuberculosis, 110
model organisms for research, 140
multi-drug resistant (MDR), 111–112
prophylatic isoniazid treatment, 68
testing for exposure to, 109
transmission of, 178
treatment of, 110–111
vaccination against, 109
N
nalidixic acid, 50
narrow-spectrum antibiotics, 32
National Healthcare Safety Network (NHSN), 128
natural sources of antibiotics, 141–142
Neisseria gonorrhoeae, 11, 185
neomycin, 142
neosalvarsan, 33
neuraminidase inhibitors, 168–169
neuraminidases, 49
new classes of antibiotics, producing, 203
NHSN (National Healthcare Safety Network), 128
nonadherence to therapy, 153
norfloxacin, 50
Novick, Richard, 14
nucleic acid-based diagnosis, 128–131
nucleic acid probes, 23–24
nucleotides
overview, 209–210
pairing between complementary nucleotides, 211
nystatin, 142
O
obesity, microbiomes and, 7
ofloxacin, 50
oseltamivir (Tamiflu), 49, 168–169, 173, 179
outbreaks of resistance, response to. See surveillance
over-the-counter antifungal agents, 154
oxazolidinones, 37
P
pain, microbiomes and, 7
pandemic influenza, 170–171
Asian Flu pandemic (1957-1958), 170
H1N1 pandemic (2009), 170
Hong Kong Flu pandemic (1968-1969), 170
public health strategy, 172, 176
Spanish Flu pandemic (1918–1919), 170
Paracoccidiodes brasiliensis, 223
parasitic worms, 224
paromycin, 44
pathogen fitness, effect of resistance mutations on, 86
pathogens. See also specific pathogens
arthropod-borne pathogens, 118–120
avoiding
airborne infections, 178–182
arthropod-borne infections, 186–187
clashes between personal and public health, 177–179
food-borne diseases, 188–196
MRSA, 182–184
overview, 177
sexually transmitted infections, 185
bacteria. See bacteria
blood-borne pathogens, 121
commensals, 5
digestive-tract pathogens, 115–116
direct-contact pathogens, 116
diversity of, 17–18
establishing causal relationships with disease
Falkow’s corollaries, 27–28
Hill’s corollaries, 27
Koch’s postulates, 24–26
focus on populations, 28–29
cellular structure of, 222
fungal diseases, 222–223
immune modulators and fungal infections, 42
molds, 222
Paracoccidiodes brasiliensis, 223
structure of, 222
yeasts, 222
helminths
diseases caused by, 224
identifying clinically resistant pathogens, 9
measuring numbers of, 18–23
multiple-mode transmission, 121–122
pathogen diversity, 5
protozoa
diseases caused by, 4, 223–224
transmission of, 5
vaccine-resistant pathogens, 13
viruses. See viruses
zoonotic pathogens, 5
PCR (polymerase chain reaction), 213–215
pentamidine, 44
persisters, 28
personal health, clashes with public health, 177–179
pertussis (whooping cough), 14
Peru, antituberculosis program in, 61–62
pharmacodynamics, 62–65
pharmacokinetic mismatch and resistance, 162
phenotypic resistance, 84
phosphonates, 103
pigs, MRSA in, 184
PK/PD (pharmacokinetics/ pharmacodynamics) indices, 62–65
combining MPC with PK/PD targets, 160–161
Plasmodium falciparum, 118
Plasmodium knowlesi, 118
Plasmodium malariae, 118
Plasmodium ovale, 118
Plasmodium vivax, 118
pneumonia, 11
bacterial pneumonia, 175
Klebsiella pneumoniae, 121–122
polymerase, 211
polymerase chain reaction (PCR), 213–215
polymerase inhibitors, 47
polymers, 208
populations, focus on, 28–29
poultry, removal of fluoroquinolones from, 133–134
prevalence of antibiotic resistance, 9–11
prokaryotic organisms, 221
Prontosil Red, 34
prophylaxis, 67–68
protective clothing, virus transfer from, 181
protein synthesis, antibacterial action on, 37
proteins
gyrase A, 82
LexA, 79
MfpA, 83
overview, 208–209
repressors, 216
protozoa
diseases caused by, 4, 223–224
Pseudomonas aeruginosa, 80
public health, clashes with personal health, 177–179
puromycin, 142
pyrazinamide, 110
pyrethrum, 187
Q
quarantine for influenza, 179
quaternary ammonium compounds, 53
quinacrine, 43
quinine, 43–44
quorum sensing, 28
R
recombination, 92–93
relaxase, 103
repressors, 216
reproduction
of bacteria, 221
of yeasts, 222
research, importance of, 205
resistance
antiseptic and disinfectant use, 84
explained, 73
horizontal gene transfer
addiction modules, 95
cassette integration, 92
explained, 91–92
gene mobilization, 99
genomic islands, 102–103
integrons, 101–102
plasmids, 94
recombination, 92–93
relaxase, 103
transformation, 98
molecular mechanisms, 80–82
mutations
effect on pathogen fitness, 86
explained, 74–75
fluoroquinolone-resistant gyrase mutants, 82
induced mutations, 79–80
mutant selection window hypothesis, 77–79
mutator mutations and increased mutation frequency, 83
phenotypic resistance, 84
resistance emerging in individual patients, 73–74, 196–197
stepwise selection of, 75–76
treatment time and, 82–83
unintended damage arising from treatment, 87–88
viral resistance, 84–86
resistant disease transmission. See transmission of resistant disease
resistant pathogens, avoiding
airborne infections, 178–182
arthropod-borne infections, 186–187
clashes between personal and public health, 177–179
food-borne diseases, 188–196
MRSA, 182–184
overview, 177
sexually transmitted infections, 185
response to disease outbreaks. See surveillance
restricting antibiotic use. See also dosing strategies
agricultural use, 155
consideration of resistance during drug discovery, 163–164
environmental contamination by antibiotics, 155–157
human consumption
correlation between human consumption of antibiotics and resistance, 150–152
limiting, 152–154
ribavirin, 46
ribonucleic acid. See RNA
ricin, 37
rickettsia, 119–120
rifampicin, 39, 52, 110, 162, 216
rifamycin, 142
rimantadine, 168
mRNA, 37
overview, 215–218
rRNA, 37
tRNA, 37
Russia, training TB workers in, 112
S
S. aureus. See MRSA (methicillin-resistant Staphylococcus aureus)
salicylic acid, 142
salvorsan, 33
SARS (severe acute respiratory syndrome), 114, 181
seasonal influenza virus
antiviral resistance to, 168–170
vaccination against, 167–168
self-medication, 69–70, 154, 197
severe acute respiratory syndrome (SARS), 114, 181
sexually transmitted infections, avoiding, 185
Shigella, 192
sickle cell disease, 224
sickle-cell trait, 223
side effects of antibiotics, 66–67, 145–146, 200–201
Silent Spring (Carson), 187
site-specific recombination, 92
sleeping sickness, 44
solutions for antibiotic resistance
drug discovery process, 204
education, 203
European MRSA initiatives, 204
higher dosage levels, 204
limited agricultural use of antibiotics, 203
lower environmental levels of antibiotics, 204
new classes of antibiotics, 203
research, 205
SOS response, 79
Spanish Flu pandemic (1918–1919), 170
Speaker, Andrew, 178
specialized transduction, 98
spontaneous mutations, 74–75
Staphylococcus aureus. See MRSA (methicillin-resistant Staphylococcus aureus)
static action of antibiotics, measuring, 20–21
static compounds, 31
stepwise selection of resistance, 75–76
Sterling Drug Company, 34
Strategic National Stockpile, 172
Streptococcus pneumoniae, 13
Streptomyces, 142
Streptomyces aureofaciens, 155
sugars, 218–219
sulbactam, 81
sulfa drugs (sulfonamides), 31, 34, 39–40
surgical masks, 180
denominator effect and surveillance accuracy, 126–127
explained, 125
as first line of defense, 125–126
genotyping, 130–131
groups performing surveillance, 127
importance of, 137
interpretation of surveillance studies, 132
nucleic acid-based diagnosis, 128–131
and removal of fluoroquinolones from U.S. poultry use, 133–134
and studies of resistance problems with gonorrhea, 133
surveillance in Danish food animals, 135
surveillance networks for antibiotic resistance, 128
susceptibility testing, 57–60
T
Tamiflu (oseltamivir), 49, 168–169, 173, 179
tazobactam, 81
TEM enzyme, 81
testing
for M. tuberculosis exposure, 109
immunological/biological testing, 62
susceptibility testing, 57–60
Theory of Febrile Diseases and Synopsis of the Golden Cabinet (Zhang), 142
ticks, and spread of Lyme disease, 120
tobramycin, 38
tolnaftate, 43
Tomasz, Alexander, 14
toxic side effects, determining, 66–67, 200
transfer RNA (tRNA), 216–217
transformation, 98
transmission of resistant disease, 5
airborne viruses, 114
arthropod-borne pathogens, 118–120
blood-borne pathogens, 121
controlling infections spread by contact in hospitals, 123
digestive-tract pathogens, 115–116
direct-contact pathogens, 116
explained, 105
infection control as local crisis management, 106–107
MRSA, 117
multiple-mode transmission, 121–122
tuberculosis, 108–113
virus transfer from protective clothing, 181
Treatise on Differentiation and Treatment of Seasonal Febrile Diseases (Wu), 142
children, 65–66
dosing strategies, 15
antibiotic concentrations above MPC, 159–160
changing dosage levels, 204
combination therapy, 162–163
combining MPC with PK/PD targets, 160–161
determining with PK/PD (pharmacokinetics/pharmacodynamics) indices, 62–65
dosing to eradicate susceptible cells, 158–159
duration of treatment, 67
empiric therapy, 55–56
immunological/biological testing, 62
management programs to control hospital antibiotic policy, 68–69
PK/PD (pharmacokinetics/ pharmacodynamics) indices, 62–65
prophylaxis, 67–68
risk for subsequent resistance, 200
self-medication, 69–70
susceptibility testing, 57, 59–60
toxic side effects, determining, 66–67
tuberculosis, 110–111
unintended damage arising from treatment, 87–88
treatment time and emergence of resistance, 82–83
Treponema pallidum, 33
triazoles, 41
trichlosan, 199
tRNA (transfer RNA), 37, 216–217
trovafloxacin, 50
trypanosomes, 44
antituberculosis agents, 52
antituberculosis program in Peru, 61–62
completely drug-resistant tuberculosis (CDR-TB), 111
determining antibiotic resistance by genotyping, 130–131
disease transmission, 108–113
extensively resistant (XDR) tuberculosis, 111, 113
in HIV-positive persons, 111
in homeless populations, 113
latent tuberculosis, 110
model organisms for research, 140
multi-drug resistant (MDR), 111–112
prophylatic isoniazid treatment, 68
testing for exposure to, 109
transmission of, 178
treatment of, 110–111
vaccination against, 109
types of antibiotic resistance, 12
typhus, 119
U
U.S. poultry, removal of fluoroquinolones from, 133–134
unintended damage arising from treatment, 87–88
V
vaccines
explained, 13
against seasonal influenza virus, 167–168
against tuberculosis, 109
vaccine-resistant pathogens, 13
vaginal yeast infections, 154
valley fever, 223
vancomycin-resistant Entercococcus faecium, 115
vancomycin-resistant enterococci (VRE), 135–136
viral resistance, 84–86
airborne viruses, 114
antiviral classes and resistance mechanisms, 45–46
cellular structure of, 224
detecting viral antibiotic resistance, 174–175
explained, 4
herpes virus, 49–50
HIV (human immunodeficiency virus), 25, 46–48, 85–86, 224
influenza
antiviral resistance to seasonal influenza, 168–170
avian flu H5N1, 171–174
avoiding, 179–180
bacterial pneumonia associated with, 175
membrane protein-2 (M2), 168
pandemic influenza, 170–172, 176
quarantine, 179
vaccination against seasonal influenza virus, 167–168
life cycle, 224
SARS (severe acute respiratory syndrome), 114, 181
virus transfer from protective clothing, 181
West Nile Virus, 120
VITEK, 59
VRE (vancomycin-resistant enterococci), 135–136
W
water, antibiotic contamination of, 156
whooping cough, 14
widespread nature of antibiotic resistance, 9–11
World Health Organization, 127
worms (parasitic), 224
Wu Jutong, 142
X
X-ray crystallography, 144
XDR (extensively resistant) tuberculosis, 111–113
Y
yeasts, 17
Candida albicans, 154
defined, 222
explained, 4
reproduction, 222
yellow fever, 120
Z
zanamivir, 168
Zhang Zhongjing, 142
zoonotic pathogens, 5