TREATMENT Shigellosis ANTIBIOTIC SUSCEPTIBILITY OF SHIGELLA
As an enteroinvasive disease, shigellosis requires antibiotic treatment. Since the mid-1960s, however, increasing resistance to multiple drugs has been a dominant factor in treatment decisions. Resistance rates are highly dependent on the geographic area. Clonal spread of particular strains and horizontal transfer of resistance determinants, particularly via plasmids and transposons, contribute to multidrug resistance. The current global status—i.e., high rates of resistance to classic first-line antibiotics such as amoxicillin—has led to a rapid switch to quinolones such as nalidixic acid. However, resistance to such early-generation quinolones has also emerged and spread quickly as a result of chromosomal mutations affecting DNA gyrase and topoisomerase IV; this resistance has necessitated the use of later-generation quinolones as first-line antibiotics in many areas. For instance, a review of the antibiotic resistance history of Shigella in India found that, after their introduction in the late 1980s, the second-generation quinolones norfloxacin, ciprofloxacin, and ofloxacin were highly effective in the treatment of shigellosis, including cases caused by multidrug-resistant strains of S. dysenteriae type 1. However, investigations of subsequent outbreaks in India and Bangladesh detected resistance to norfloxacin, ciprofloxacin, and ofloxacin in 5% of isolates. The incidence of multidrug resistance parallels the widespread, uncontrolled use of antibiotics and calls for the rational use of effective drugs. ANTIBIOTIC TREATMENT OF SHIGELLOSIS
Because of the ready transmissibility of Shigella, current public health recommendations in the United States are that every case be treated with antibiotics (Table 63-1). Ciprofloxacin is recommended as first-line treatment. A number of other drugs have been tested and shown to be effective, including ceftriaxone, azithromycin, pivmecillinam, and some fifth-generation quinolones. Whereas infections caused by non-dysenteriae Shigella in immunocompetent individuals are routinely treated with a 3-day course of antibiotics, it is recommended that S. dysenteriae type 1 infections be treated for 5 days and that Shigella infections in immunocompromised patients be treated for 7–10 days.
Treatment for shigellosis must be adapted to the clinical context, with the recognition that the most fragile patients are children <5 years old, who represent two-thirds of all cases worldwide. There are few data on the use of quinolones in children, but Shigella-induced dysentery is a well-recognized indication for their use. The half-life of ciprofloxacin is longer in infants than in older individuals. The ciprofloxacin dose generally recommended for children is 30 mg/kg per day in two divided doses. Adults living in areas with high standards of hygiene are likely to develop milder, shorter-duration disease, whereas infants in endemic areas can develop severe, sometimes fatal, dysentery. In the former setting, treatment will remain minimal and bacteriologic proof of infection will often come after symptoms have resolved; in the latter setting, antibiotic treatment and more aggressive measures, possibly including resuscitation, are often required. REHYDRATION AND NUTRITION
Shigella infection rarely causes significant dehydration. Cases requiring aggressive rehydration (particularly in industrialized countries) are uncommon. In developing countries, malnutrition remains the primary indicator for diarrhea-related death, highlighting the importance of nutrition in early management. Rehydration should be oral unless the patient is comatose or presents in shock. Because of the improved effectiveness of reduced-osmolarity oral rehydration solution (especially for children with acute noncholera diarrhea), the WHO and UNICEF now recommend a standard solution of 245 mOsm/L (sodium, 75 mmol/L; chloride, 65 mmol/L; glucose [anhydrous], 75 mmol/L; potassium, 20 mmol/L; citrate, 10 mmol/L). In shigellosis, the coupled transport of sodium to glucose may be variably affected, but oral rehydration therapy remains the easiest and most efficient form of rehydration, especially in severe cases.
Nutrition should be started as soon as possible after completion of initial rehydration. Early refeeding is safe, well tolerated, and clinically beneficial. Because breast-feeding reduces diarrheal losses and the need for oral rehydration in infants, it should be maintained in the absence of contraindications (e.g., maternal HIV infection). NONSPECIFIC, SYMPTOM-BASED THERAPY
Antimotility agents have been implicated in prolonged fever in volunteers with shigellosis. These agents are suspected of increasing the risk of toxic megacolon and are thought to have been responsible for HUS in children infected by EHEC strains. For safety reasons, it is better to avoid antimotility agents in bloody diarrhea. TREATMENT OF COMPLICATIONS
There is no consensus regarding the best treatment for toxic megacolon. The patient should be assessed frequently by both medical and surgical teams. Anemia, dehydration, and electrolyte deficits (particularly hypokalemia) may aggravate colonic atony and should be actively treated. Nasogastric aspiration helps to deflate the colon. Parenteral nutrition has not been proven to be beneficial. Fever persisting beyond 48–72 h raises the possibility of local perforation or abscess. Most studies recommend colectomy if, after 48–72 h, colonic distention persists. However, some physicians recommend continuation of medical therapy for up to 7 days if the patient seems to be improving clinically despite persistent megacolon without free perforation. Intestinal perforation, either isolated or complicating toxic megacolon, requires surgical treatment and intensive medical support.
Rectal prolapse must be treated as soon as possible. With the health care provider using surgical gloves or a soft warm wet cloth and the patient in the knee-chest position, the prolapsed rectum is gently pushed back into place. If edema of the rectal mucosa is evident (rendering reintegration difficult), it can be osmotically reduced by the application of gauze impregnated with a warm solution of saturated magnesium sulfate. Rectal prolapse often relapses but usually resolves along with the resolution of dysentery.
HUS must be treated by water restriction, including discontinuation of oral rehydration solution and potassium-rich alimentation. Hemofiltration is usually required.