From Alzheimer’s to Zebrafish: Eclectic Science and Regulatory Stories 28
For more than 50 years, pharmacists have dispensed antibiotics to treat infections caused
by bacteria and other microorganisms. After their discovery in 1928, antibiotics rapidly
grew in number and potency, causing doctors and scientists to almost entirely disregard
the challenge of treating bacterial diseases.1 However, much has changed since then, as
bacterial resistance now undermines the efficacy of antimicrobial agents.
The misuse and overuse of antibiotics have resulted in a continuous evolution of bac-
teria resistant to the drugs that were previously able to control them. Bacterial resistance
was demonstrated when penicillin was first administered during clinical trials. Initial
cultures of Penicillium were contaminated with Escherichia coli (E. coli), which produced
an enzyme that degraded penicillin. In the second clinical trial in 1943, one of 15 patients
died from a streptococcal infection after E. coli had become resistant to the antibiotic.2 Soon
after, a description of penicillinase-producing strains of Staphylococcus aureus was pub-
lished in 1944, and scientists learned that bacteria could become resistant to penicillin.3
Other bacteria have shown antibiotic resistance. For example, clinicians have tried
to control the spread of methicillin-resistant S. aureus (MRSA) bacteria since it was first
identified in the 1960s. In the mid-1970s, Haemophilus influenzae and Neisseria gonorrhoeae
became resistant to penicillin. Even vancomycin, often the antibiotic of last resort, is in
jeopardy in 2002, a vancomycin-resistant S. aureus (VRSA) isolate was recovered from a
hospital patient in Michigan. The resistant determinant may have been acquired through
the exchange of genetic material from a vancomycin-resistant enterococcus.
Researchers now know that antibiotic-resistant genes existed long before humans
began developing and using antibiotics.4 Bacteria that create antibiotics are protected by
genes that make them resistant to the antibiotics they produce. Some bacteria that do not
produce antibiotics also have resistant genes. As a result, many researchers are predicting
a return to the pre-antibiotic era in which only supportive treatment would be available
to manage infections. While the evolution of bacteria toward resistance to antimicrobial
drugs represents the general evolution of bacteria that is unstoppable, much can be done
to delay the subsequent spread of antibiotic resistance.5
How Widespread Is Bacterial Resistance?
There has been an alarming rise in resistant (often multi-drug-resistant) hospital- and
community-acquired bacteria during the past two decades both in the US and world-
wide.6 Currently, every country in the world is plagued with drug-resistant diseases such
as gonorrhea and lethal staphylococcal infections.7 According to the Public Health Action
Plan published in 2000, drug-resistant pathogens are a growing menace to all people,
regardless of age, gender or socioeconomic background.8
Resistance increases and occurs more rapidly with bacteriostatic agents (e.g., tetra-
cyclines, sulfonamides, macrolides) than with bactericidal drugs (e.g., aminoglycosides,
beta-lactams).9 Antimicrobial resistance is also more likely to emerge when widespread
usage is combined with suboptimal dosage.10
Several clinically important microbes have developed resistance to available antimi-
crobials, such as Streptococcus pneumoniae (pneumonia, ear infections and meningitis), S.
aureus and Pseudomonas aeruginosa (skin, bone, lung and bloodstream infections), E. coli
(urinary tract infections), Salmonella (foodborne infections) and Enterococcus and Klebsiella
spp. (infections transmitted in healthcare settings).
Up to 30% of S. pneumoniae strains found in some parts of the US are no longer sus-
ceptible to penicillin, and multi-drug resistance is common. Approximately 11% of these
strains are resistant to third-generation cephalosporins, and resistance to fluoroquinolones
has occurred. In addition, nearly all strains of S. aureus in the US are resistant to penicil-
lin, many are resistant to newer methicillin-related drugs and some have a decreased
susceptibility to vancomycin. Many other pathogens, such as HIV, the bacteria that cause
For more than 50 years, pharmacists have dispensed antibiotics to treat infections caused
by bacteria and other microorganisms. After their discovery in 1928, antibiotics rapidly
grew in number and potency, causing doctors and scientists to almost entirely disregard
the challenge of treating bacterial diseases.1 However, much has changed since then, as
bacterial resistance now undermines the efficacy of antimicrobial agents.
The misuse and overuse of antibiotics have resulted in a continuous evolution of bac-
teria resistant to the drugs that were previously able to control them. Bacterial resistance
was demonstrated when penicillin was first administered during clinical trials. Initial
cultures of Penicillium were contaminated with Escherichia coli (E. coli), which produced
an enzyme that degraded penicillin. In the second clinical trial in 1943, one of 15 patients
died from a streptococcal infection after E. coli had become resistant to the antibiotic.2 Soon
after, a description of penicillinase-producing strains of Staphylococcus aureus was pub-
lished in 1944, and scientists learned that bacteria could become resistant to penicillin.3
Other bacteria have shown antibiotic resistance. For example, clinicians have tried
to control the spread of methicillin-resistant S. aureus (MRSA) bacteria since it was first
identified in the 1960s. In the mid-1970s, Haemophilus influenzae and Neisseria gonorrhoeae
became resistant to penicillin. Even vancomycin, often the antibiotic of last resort, is in
jeopardy in 2002, a vancomycin-resistant S. aureus (VRSA) isolate was recovered from a
hospital patient in Michigan. The resistant determinant may have been acquired through
the exchange of genetic material from a vancomycin-resistant enterococcus.
Researchers now know that antibiotic-resistant genes existed long before humans
began developing and using antibiotics.4 Bacteria that create antibiotics are protected by
genes that make them resistant to the antibiotics they produce. Some bacteria that do not
produce antibiotics also have resistant genes. As a result, many researchers are predicting
a return to the pre-antibiotic era in which only supportive treatment would be available
to manage infections. While the evolution of bacteria toward resistance to antimicrobial
drugs represents the general evolution of bacteria that is unstoppable, much can be done
to delay the subsequent spread of antibiotic resistance.5
How Widespread Is Bacterial Resistance?
There has been an alarming rise in resistant (often multi-drug-resistant) hospital- and
community-acquired bacteria during the past two decades both in the US and world-
wide.6 Currently, every country in the world is plagued with drug-resistant diseases such
as gonorrhea and lethal staphylococcal infections.7 According to the Public Health Action
Plan published in 2000, drug-resistant pathogens are a growing menace to all people,
regardless of age, gender or socioeconomic background.8
Resistance increases and occurs more rapidly with bacteriostatic agents (e.g., tetra-
cyclines, sulfonamides, macrolides) than with bactericidal drugs (e.g., aminoglycosides,
beta-lactams).9 Antimicrobial resistance is also more likely to emerge when widespread
usage is combined with suboptimal dosage.10
Several clinically important microbes have developed resistance to available antimi-
crobials, such as Streptococcus pneumoniae (pneumonia, ear infections and meningitis), S.
aureus and Pseudomonas aeruginosa (skin, bone, lung and bloodstream infections), E. coli
(urinary tract infections), Salmonella (foodborne infections) and Enterococcus and Klebsiella
spp. (infections transmitted in healthcare settings).
Up to 30% of S. pneumoniae strains found in some parts of the US are no longer sus-
ceptible to penicillin, and multi-drug resistance is common. Approximately 11% of these
strains are resistant to third-generation cephalosporins, and resistance to fluoroquinolones
has occurred. In addition, nearly all strains of S. aureus in the US are resistant to penicil-
lin, many are resistant to newer methicillin-related drugs and some have a decreased
susceptibility to vancomycin. Many other pathogens, such as HIV, the bacteria that cause