Shigellosis Medication

Shigella infection produces a self-limited diarrheal illness that lasts 5-7 days and may not require antibiotics in individuals who are otherwise healthy. Antibiotic treatment is recommended for infirm or older patients, malnourished children, patients infected with HIV, food handlers, health care workers, and children in day care centers.^[6]

For public health reasons, most experts recommend treating any person whose stool culture is positive for Shigella species. Moreover, antibiotics have been shown to decrease the duration of fever and diarrhea by about 2 days. The shorter duration of shedding with antibiotic therapy can reduce the risk of person-to-person spread.

Ampicillin was widely used in the past but is no longer an effective empiric treatment in the United States because of antibiotic resistance.^[8] In fact, antibiotic resistance to Shigella species is widespread and increasing worldwide. Thus, antibiotic susceptibility testing is essential for the management of patients with suspected Shigella infection.

Given the widespread resistance to ciprofloxacin as well as trimethoprim-sulfamethoxazole and azithromycin, a third-generation cephalosporin is appropriate empiric therapy in the setting of acute illness.^{[6, 9]} The treatment of choice for HIV-infected patients is a quinolone for 5 days.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.^[10]

Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Bactericidal activity results from inhibiting cell wall synthesis by binding to one or more penicillin binding proteins. Exerts antimicrobial effect by interfering with synthesis of peptidoglycan, a major structural component of bacterial cell wall. Bacteria eventually lyse due to the ongoing activity of cell wall autolytic enzymes while cell wall assembly is arrested.

Highly stable in presence of beta-lactamases, both penicillinase and cephalosporinase, of gram-negative and gram-positive bacteria. Approximately 33-67% of dose excreted unchanged in urine, and remainder secreted in bile and ultimately in feces as microbiologically inactive compounds. Reversibly binds to human plasma proteins, and binding have been reported to decrease from 95% bound at plasma concentrations < 25 mcg/mL to 85% bound at 300 mcg/mL.

Ciprofloxacin (Cipro)

Fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth.

Trimethoprim-sulfamethoxazole (Bactrim, Septra, Bactrim DS, Cotrim)

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Reasonable DOC in the United States due to few resistant strains.

Dosing may be based on TMP component.

Azithromycin (Zithromax)

Acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected.

Concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.

Treats mild-to-moderate microbial infections.

Plasma concentrations are very low, but tissue concentrations are much higher, giving it value in treating intracellular organisms. Has a long tissue half-life.