Shigella Infection Medication

Various antimicrobial agents are effective in the treatment of shigellosis, although options are becoming limited because of globally emerging drug resistance. Resistance of Shigella species to sulfonamides, tetracyclines, ampicillin, and trimethoprim-sulfamethoxazole (TMP-SMX) has been reported worldwide, and these agents are not recommended as empirical therapy. Most clinical infections with S sonnei are self-limited (48-72 h) and may not require antimicrobial therapy.

If an ampicillin and TMP-SMX resistant strain is isolated or if susceptibility is unknown, parenteral ceftriaxone sodium, fluoroquinolone (eg, ciprofloxacin, ofloxacin), azithromycin dihydrate (off-label indication), or cefixime are the drugs of choice.^{[4, 5]} Fluoroquinolones are typically not administered to children and adolescents younger than 18 years unless other antibiotic choices are not suitable.

Because shigellosis is self-limiting, some authorities recommend withholding antibiotic therapy. However, even if not fatal, the untreated illness may cause chronic or recurrent diarrhea, making a child quite ill for several weeks; this may lead to malnutrition, especially in developing countries. The risk of continued shedding of organisms in stool increases the risk of transmission of further disease among contacts argues against withholding antimicrobial treatment.

Presently, no US Food and Drug Administration (FDA)–approved vaccines are available.

Antimicrobial therapy is typically administered for 5 days. Antibiotic treatment decreases the duration of illness, person-to-person spread, and cases in household contacts. Treatment in malnourished children (eg, in developing countries) is likely to reduce the risk of worsening malnutrition morbidity after shigellosis. In persons infected with S dysenteriae type 1, early administration of effective antibiotics decreases Stx concentrations in the stool and lowers HUS risk. However, the risk of HUS caused by E coli O157-H7 may be increased with the early administration of antibiotics. Prophylactic antibiotics are not recommended for contacts.

Antidiarrheal medications (diphenoxylate hydrochloride with atropine [Lomotil] or loperamide [Imodium]) should not be used because of the risk of prolonging the illness.

A child with typical dysentery that responds to initial empirical antibiotic treatment should continue taking the same drug for a full 5-day course, even if the stool culture is negative.

Nutritional supplementation including vitamin A (200,000 IU) and zinc (20 mg/d for 14 d)^[6] may be administered to hasten the clinical recovery and immune response in the settings of malnutrition or in certain geographic areas.

Class Summary

Ampicillin and TMP-SMZ are effective for susceptible strains; amoxicillin is less effective than this because of its rapid absorption high in the GI tract. The oral route is preferred except for seriously ill patients. In the United States, sentinel surveillance data from 2003-2006 indicated that 94% of S sonnei and 67% of S flexneri organisms were resistant to ampicillin and TMP-SMZ. Ampicillin (but not amoxicillin) is still the drug of choice if the isolate is susceptible to this drug.

Ampicillin (Principen)

Broad-spectrum penicillin. Interferes with bacterial cell-wall synthesis during active replication, causing bactericidal activity against susceptible organisms.

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.

Trimethoprim and sulfamethoxazole (Bactrim, Cotrim)

Combination effective for shigellosis. Produces sequential blockade in folic acid synthesis. Effect frequently synergistic and bactericidal.

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. It has enhanced activity against gram-negative organisms. Concentrates in phagocytes and fibroblasts, as demonstrated with in vitro incubation techniques; hence, plasma concentrations are very low but tissue concentrations are very high. It has a long tissue half-life and once daily dosage is recommended. In vivo data suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.

Cefixime (Suprax)

Third-generation oral cephalosporin with broad activity against gram-negative bacteria. By binding to one or more of the penicillin-binding proteins, it arrests bacterial cell wall synthesis and inhibits bacterial growth. For outpatient use in drug-resistant Shigella infections.

Ciprofloxacin (Cipro)

Fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth, by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Has no activity against anaerobes. Continue treatment for at least 2 d (7-14 d typical) after signs and symptoms have disappeared.

Nalidixic acid (NegGram)

First-generation quinolone. Blocks bacterial DNA gyrase. Useful in patients with sulfas and cephalosporin allergy.