Typhoid fever is treated with antibiotics that kill the Salmonella bacteria. Prior to the use of antibiotics, the fatality rate was 20%. Death occurred from overwhelming infection, pneumonia, intestinal bleeding, or intestinal perforation. With antibiotics and supportive care, mortality has been reduced to 1%-2%. With appropriate antibiotic therapy, there is usually improvement within one to two days and recovery within seven to 10 days.

Several antibiotics are effective for the treatment of typhoid fever. Chloramphenicol was the original drug of choice for many years. Because of rare serious side effects, chloramphenicol has been replaced by other effective antibiotics. The choice of antibiotics needs to be guided by identifying the geographic region where the organism was acquired and the results of cultures once available. (Certain strains from South America show a significant resistance to some antibiotics.) Ciprofloxacin (Cipro) is the most frequently used drug in the U.S. for nonpregnant patients. Ceftriaxone (Rocephin), an intramuscular injection medication, is an alternative for pregnant patients. Ampicillin (Omnipen, Polycillin, Principen) and trimethoprim-sulfamethoxazole (Bactrim, Septra) are frequently prescribed antibiotics although resistance has been reported in recent years. If relapses occur, patients are retreated with antibiotics.

The carrier state, which occurs in 3%-5% of those infected, can be treated with prolonged antibiotics. Often, removal of the gallbladder, the site of chronic infection, will cure the carrier state.