Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Sulfa drugs

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sive infection. However, about half of those who are infected

will transmit the bacteria to their babies during delivery.

In the United States, about 12,000 newborns will be

infected each year. Of these, about 8,000 develop early-onset

infection within hours or days of birth. Complications

include inflammationof the membranes covering the brain

and spinal cord (meningitis), pneumonia, and blood infection

(sepsis). In other infants, meningitis will develop in the first

three months of life.

The streptococci in group D are a common cause of

wound infections in hospital patients. As well, group D strep-

tococci are associated with abnormal growth of tissue in the

gastrointestinal tract, urinary tract infection, and infections of

the womb in women who have just given birth.

Another group of the streptococci that is of concern to

human health is group G. Normally present on the skin, in the

mouth and throat, and in the intestines and genital tract, group

G streptococci can cause opportunistic infections in people

whose immune systems are compromised by disease, therapy,

or neglect. Candidates for infection include severe alcoholics,

those with cancer, diabetes mellitus, and rheumatoid arthritis.

The bacteria of this group can cause a variety of infections,

including infection of the bloodstream (bacteremia), inflam-

mation of the connective tissue structure surrounding a joint

(bursitis), infection of various regions of the heart and heart

valves (endocarditis), meningitis, inflammation of bone and

bone marrow (osteomyelitis), and the inflammation of the lin-

ing of the abdomen (peritonitis).

The conventional treatment for streptococcal infections

is the administration of antibiotics. Many strains of strep are

still susceptible to penicillin. However, strains of Streptococcus

pneumoniathat are resistant to multiple antibiotics are a prob-

lem in hospitals world-wide.

Prevention of infection involves keeping wounds clean

and good hygienic practices, such as frequent hand washing,

especially before eating and after using the bathroom.

See alsoBacteria and bacterial infection

STREPTOMYCIN•seeANTIBIOTICS

SSulfa drugsULFA DRUGS

Sulfa drugs, developed in the 1930s, were the first medica-

tions effective against bacterial disease. They appeared as the

first “miracle drugs” at a time when death from bacterial infec-

tions such as pneumoniaand blood poisoning were common.

In 1932, German physician and biomedical researcher

Gerhard Domagk was working on a project for the German

industrial giant I. G. Farbenindustrie to test industrial chemi-

cals for medical utility. One of the chemicals was a dye called

Prontosil, or sulfamidochrysoidine. Domagk hypothesized

that since the dye worked by binding to the proteins in fabric

and leather, it might also bind to the proteins in bacteria, thus

inhibiting their action. Experiments on laboratory animals

infected with streptococcus were promising, and were soon

followed by successful clinical tests.

In 1936, Prontosil was successfully used against puer-

peral sepsis, or “childbed fever,” which was killing thousands

of mothers every year. It was also shown to be effective

against meningitis, pneumonia, and streptococcal infections.

Meanwhile, scientists at the Pasteur Institute in Paris

discovered that upon ingestion, the dye molecule was cleaved

in two, and that the active part, sulfanilamide, was just as

effective on its own. This was important because the smaller

molecule was not covered by Farben’s patent on Prontosil, and

was also less expensive to produce.

There followed a rush by pharmaceutical companies in

the United States and Europe to develop sulfa drugs of their

own. Among the most effective were sulfapyridine for pneu-

monia, sulfathiazole against pneumonia and staphylococcus,

sulfaguanadine to treat dysentery, and sulfadiazine, which

worked against pneumonia, strep and staph. Domagk was

awarded the Nobel Prize in Medicine in 1939, but World War

II prevented him from receiving his medal until 1947.

Investigating the action of the sulfa drugs led to an

important new understanding of the action of pharmaceuticals.

Sulfanilamides compete with the action of para-aminobenzoic

acid (PABA), which bacteria use to produce folic acid.

Without folic acid, the bacteria cannot synthesize DNA. This is

an example of a common drug mechanism called antagonism.

A structurally similar molecule can work against a substance

necessary to the metabolismof a microorganism (or involved

in some other disease process) by competitively binding to the

same enzyme and thus blocking its action.

A tragic episode involving a sulfa drug was also impor-

tant in medical history because of its effect on United States

law. In 1937, the S. E. Massengill Company released a sulfa

medication in liquid form. Unfortunately, a toxic solvent (the

medium suspending the sulfa medication) was used, and more

than 100 people died. The next year, the Federal Food, Drug

and Cosmetics Act was passed, requiring that new drugs be

tested for safety.

The ability to fight dysentery and other bacterial dis-

eases with sulfa drugs was important to soldiers in World War

II. However, too much sulfa was bad for the kidneys, and by

the end of the war, penicillinand other newly developed antibi-

oticswith fewer side effects became increasingly available

and preferred in treatment. In addition, many bacterial strains

have developed resistance against sulfa drugs in the decades

since they were developed, which has also limited their use-

fulness. Regardless, they are still effective against some infec-

tions, including leprosy, and are often used in developing

nations because of their low cost.

See alsoAntibiotic resistance, tests for; Antibiotics; Bacteria

and bacterial infection; Bioterrorism, protective measures;

History of the development of antibiotics; History of public

health; Infection and resistance; Penicillin; Streptococci and

streptococcal infections

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