Shigella infection: Treatment and prevention in adults

INTRODUCTION — Shigella species are a common cause of bacterial diarrhea worldwide.

The treatment and prevention Shigella infection in adults will be reviewed here. The epidemiology, microbiology, clinical manifestations, and diagnosis of Shigella, as well as the management of Shigella infection in children, are discussed separately. (See "Shigella infection: Epidemiology, clinical manifestations, and diagnosis" and "Shigella infection: Treatment and prevention in children".)

NATURAL HISTORY OF INFECTION — Infection with Shigella is generally self-limited; the average duration of symptoms associated with untreated Shigella gastroenteritis is seven days [1]. In the absence of antibiotic treatment, patients with Shigella gastroenteritis may shed the organism for up to six weeks after the resolution of symptoms; risk factors for asymptomatic shedding are not known.

Complications of Shigella gastroenteritis, including bacteremia and severe colonic disease resulting in obstruction or perforation, are rare in immunocompetent adults. However, individuals with underlying immunodeficiency (including human immunodeficiency virus [HIV] infection) or malnutrition are at increased risk for complications and worse outcomes associated with Shigella infection. (See "Shigella infection: Epidemiology, clinical manifestations, and diagnosis".)

MICROBIOLOGY

Shigella species — Among Shigella species causing infection in the United States, S. sonnei is most common, particularly among children, and S. flexneri is the next most common. Disease caused by S. sonnei tends to be less severe than that caused by S. flexneri. S. dysenteriae occurs only in individuals with international exposure, and S. boydii is currently limited to the Indian subcontinent.

Species of Shigella and epidemiologic burden of disease are discussed separately. (See "Shigella infection: Epidemiology, clinical manifestations, and diagnosis", section on 'Microbiology' and "Shigella infection: Epidemiology, clinical manifestations, and diagnosis", section on 'Burden of disease'.)

Antibiotic resistance — Shigella species have emerged with resistance to several antibiotics, including fluoroquinolones, cephalosporins and azithromycin [2]. The major route for dissemination of resistance is via horizontal transfer of plasmids carrying antibiotic resistance genes [3-6].

●Risk factors – Antibiotic-resistant Shigella infections have been observed more frequently among the following patient groups:

•Men who have sex with men (MSM) [7,8]

•People with HIV infection

•People experiencing homelessness

•Patients with infection acquired in Asia or Africa (such as in the context of international travel or adoption)

●Global epidemiology – Globally, antibiotic-resistant Shigella infections are the most common cause of moderate to severe diarrhea among children [9-11]. Antimicrobial resistance was first reported in Asia, Africa, and South America in the 1990s. In Asia and Africa, 65 to 85 percent of isolates are resistant to nalidixic acid (a quinolone) and trimethoprim-sulfamethoxazole, and 20 to 30 percent are resistant to fluoroquinolones. Resistance to nalidixic acid has also been reported in England. Resistance to azithromycin has been reported in Asia [12,13] and Europe [14]. A clone that has spread through parts of Vietnam displays resistance to third-generation cephalosporins and fluoroquinolones [15].

●Epidemiology within the United States

•Extensively drug-resistant (XDR) strains – In 2023, the United States Centers for Disease Control and Prevention (CDC) issued a health advisory regarding an increase in XDR Shigella infections reported through national surveillance systems [16]. CDC defines XDR Shigella bacteria as strains with resistance to azithromycin, ciprofloxacin, ceftriaxone, trimethoprim-sulfamethoxazole, and ampicillin.

In 2022, about 5 percent of Shigella infections reported to CDC were caused by XDR strains, compared with 0 percent in 2015. Of these, approximately 80 percent occurred in males; of these, most who provided sexual history reported male-to-male sexual contact [16]. Similar XDR Shigella isolates have been identified in England and France, largely among MSM as well as among males with recent travel to South Asia or Southeast Asia [17,18].

•Routine resistance monitoring – In the United States, among the 3079 Shigella isolates tested by the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria by whole genome sequencing during 2022, the following results were reported [19]:

-Ceftriaxone – 10.9 percent resistant

-Ciprofloxacin – 54.3 percent decreased susceptibility

-Azithromycin – 32.1 percent resistant

-Ampicillin – 67.8 percent resistant

-Trimethoprim-sulfamethoxazole – 63.3 percent resistant

-Nalidixic acid – 31.8 percent resistant

In 2022, 89 percent of isolates tested by whole genome sequencing were resistant to three or more Clinical and Laboratory Standards Institute (CLSI) antimicrobial classes [19], and 5 percent were extensively drug resistant (defined above) [20]. There are substantial differences in resistance rates among states; the NARMS data may be used to understand regional resistance rates.

•Ciprofloxacin susceptibility breakpoint – Due to an increasing proportion of Shigella isolates in the United States with ciprofloxacin minimum inhibitory concentration (MIC) >0.12 mcg/mL, in 2018 the CLSI changed the breakpoints for ciprofloxacin to the following: susceptible, MIC ≤0.12 mcg/mL; intermediate, MIC 0.25 to 0.5 mcg/mL; and resistant ≥1 mcg/mL [4]. (See 'Directed therapy' below.)

MANAGEMENT

Supportive therapy — Hydration is important to compensate for fluid loss from the gastrointestinal tract; oral rehydration is sufficient in most cases. Issues related to fluid repletion are discussed further separately. (See "Approach to the adult with acute diarrhea in resource-abundant settings", section on 'Fluid repletion'.)

We avoid antimotility agents in patients with clinical features suggestive of dysentery (fever, bloody or mucoid stools) because of concerns that antimotility agents can prolong disease in such infections or lead to more severe illness [21]. (See "Oral rehydration therapy" and "Maintenance and replacement fluid therapy in adults".)

Antibiotic treatment

Indications

Our approach — Given the evolving drug-resistance among Shigella isolates worldwide, the optimal approach to antibiotic treatment is uncertain. Here, we describe our approach and note how it differs slightly from guidance issued by the United States Centers for Disease Control and Prevention (CDC).

●Symptomatic patients – For patients with Shigella infection who are immunocompromised and/or have severe disease (characterized by bacteremia, intestinal or extraintestinal complications, or need for hospitalization), we recommend antibiotic therapy. For other symptomatic adults with Shigella infection, we suggest antibiotic therapy.

Our approach differs from the guidance issued by the CDC. (See 'Guidance from CDC' below.)

•Advantages of treatment – Antibiotic treatment may shorten the duration of fever and diarrhea by about two days [22]. In addition, antibiotic treatment may shorten the duration of pathogen shedding in stool, which may confer public health benefit by reducing the risk of person-to-person spread; however, data to support this assertion are limited. The household secondary attack rate for Shigella infection is approximately 20 percent [23]. Small, randomized trials in adults and children have demonstrated reduction in bacterial shedding with antibiotic treatment (two to five days versus up to four weeks with placebo) [22,24-27].

•Low concern for hemolytic uremic syndrome (HUS) – Antibiotic treatment of S. dysenteriae infection has not been observed to increase the incidence of HUS [28], in contrast to HUS associated with enterohemorrhagic Escherichia coli (EHEC) or Shiga toxin-producing E. coli (STEC). This may be because the mechanism that controls Shiga toxin production in S. dysenteriae is distinct from EHEC or STEC.

●Patients who are no longer symptomatic – We do not give antibiotics to patients with Shigella whose symptoms resolve prior to microbiologic diagnosis in the absence of antibiotic therapy, unless there are public health concerns (for example, the patient is a food handler and may shed Shigella organisms asymptomatically with risk for transmission to others). (See 'Natural history of infection' above.)

Guidance from CDC — Our approach differs from the guidance issued by the United States the Centers for Disease Control and Prevention (CDC), which recommends reserving antibiotic treatment for individuals in the following categories, regardless of whether the illness occurs in the context of an outbreak [4]:

●Patients who are immunocompromised (including patients with HIV infection and CD4 count <500 cells/microL).

●Patients who have severe disease characterized by bacteremia, intestinal or extraintestinal complications, or the need for hospitalization.

●Individuals who are food handlers, childcare providers, residents of nursing homes, or otherwise in settings with the potential to spread the disease. (See "Shigella infection: Epidemiology, clinical manifestations, and diagnosis".)

The CDC issued this guidance in the context of increasing fluoroquinolone MICs among Shigella isolates in the United States. (See 'Antibiotic resistance' above.)

Antibiotic selection

Empiric therapy — Issues related to empiric antibiotic therapy in the absence of stool culture data are discussed separately. (See "Approach to the adult with acute diarrhea in resource-abundant settings", section on 'Empiric antibiotic therapy'.)

For treatment of patients with Shigella infection prior to availability of antimicrobial susceptibility data, antibiotic selection should be informed by the risk of drug resistance based on patient demographics and the local resistance prevalence [19] (see 'Antibiotic resistance' above):

●For patients who have no clear risk factors for drug resistance, treatment with a fluoroquinolone is reasonable; other acceptable agents are summarized in the table (table 1).

●For individuals at risk for drug-resistant infection (including men who have sex with men, international travelers, people with HIV infection and people experiencing homelessness), the clinical approach depends on the severity of illness:

•For patients who are immunocompromised and/or have severe disease (characterized by bacteremia, intestinal or extraintestinal complications, or need for hospitalization), we suggest treatment with a carbapenem (such as ertapenem [1 g intravenous (IV) every 24 hours], imipenem [500 mg IV every 6 hours], or meropenem [1 g IV every 8 hours]).

•For patients with mild to moderate illness, initial empiric outpatient management with a fluoroquinolone is reasonable; in such cases, patients should be monitored carefully by telephone and the antibiotic regimen should be adjusted as needed once susceptibility results are available.

Directed therapy — Antibiotic therapy should be tailored to antimicrobial susceptibility results when available.

●Clinical approach

•Drug-susceptible infection – In the absence of drug-resistant infection, treatment options include a fluoroquinolone, azithromycin, or a third-generation cephalosporin (cefixime or ceftriaxone). Trimethoprim-sulfamethoxazole and ampicillin are also options if susceptibility is documented. Doses and durations are included in the table (table 1).

Fluoroquinolones, macrolides, beta-lactams, and trimethoprim-sulfamethoxazole all have established efficacy for susceptible Shigella isolates. In a systematic review of 16 trials evaluating these different antibiotic regimens, there was no consistent evidence that one particular agent was superior to the others, although the overall quality of the data was low [22].

•Drug-resistant infection – For management of infection due to drug-resistant Shigella, a carbapenem may be used; infectious disease consultation is advised.

●Susceptibility testing

•Fluoroquinolones – Ciprofloxacin susceptibility should be assessed carefully; fluoroquinolones should be avoided when the ciprofloxacin minimum inhibitory concentration (MIC) is >0.12 mcg/mL [4]. In one study including 15 patients with S. sonnei isolates with ciprofloxacin MICs of 0.12 mcg/mL, two patients experienced clinical and/or microbiological failure with ciprofloxacin treatment [3]. (See 'Antibiotic resistance' above.)

•Azithromycin – Many clinical laboratories do not routinely evaluate Shigella isolates for azithromycin susceptibility because there is no standardized testing. However, some laboratories can perform azithromycin susceptibility testing when requested; this should be done if available, especially for isolates from patients at risk for drug-resistant infection.

For Shigella species, MIC breakpoints for azithromycin are ≤8 mcg/mL for susceptible, 16 mcg/mL for intermediate, and ≥32 mcg/mL for resistant. Disc diffusion breakpoints for azithromycin are ≥16 mm for susceptible, 11 to 15 mm for intermediate, and ≤10 mm for resistant [29]. The zone of inhibition for azithromycin can be hazy and therefore difficult to interpret; when this is the case, we recommend requesting that MICs be performed.

•Other agents – Addition of susceptibility testing for carbapenems and fosfomycin is useful for patients with known or suspected drug-resistant infection [18].

Duration — The duration of treatment for Shigella infection depends on the agent used and certain patient factors (table 1). In general, fluoroquinolones and azithromycin are given for three days; beta-lactams are given for five days. However, for patients with infection due to S. dysenteriae type 1 or with HIV coinfection, five to seven days of therapy are warranted [30-32]. In the setting of bacteremia, a 14-day course is reasonable.

Follow-up — Clinical improvement (eg, less frequent stools, less blood in the stools, lower fever, improved appetite) is expected within one to two days if Shigella infection is treated with an antibiotic to which the isolate is susceptible [33,34].

If symptoms persist or worsen despite three days of treatment, repeat stool culture and susceptibility testing should be performed to evaluate for drug resistance or an alternative diagnosis.

If symptoms persist despite treatment with an antibiotic to which the isolate has demonstrated in vitro susceptibility, other potential causes should be considered; pending further evaluation, switching to another antibiotic is reasonable. (See "Approach to the adult with acute diarrhea in resource-abundant settings", section on 'Persistent diarrhea'.)

There is no role for routine follow-up stool cultures.

PREVENTION

●Patients

•General guidance – Patients with Shigella infection should be counseled on the following practices to reduce the risk of transmission:

-Stay home from school or from healthcare, food service, or childcare jobs while sick or in conjunction with guidance from local health authorities.

-Wash hands often with soap and water for at least 20 seconds, including at key times such as after using the toilet, before and after changing diapers or cleaning up after someone who is sick, and before preparing or eating food.

-Do not prepare food for others, if possible.

-Stay out of recreational water; this includes swimming pools, hot tubs, water playgrounds, oceans, lakes, and rivers.

-Follow preventive measures related to sexual activity (table 2).

•Food handlers, healthcare workers, and childcare workers – Decisions regarding follow-up evaluation and timing of safe return to work should be made in conjunction with guidance from local public health authorities; shigellosis is a nationally notifiable disease.

●Uninfected individuals – For uninfected individuals, preventive measures include frequent handwashing with soap and water, particularly after using the restroom or changing a child's diaper [35]. In childcare centers, separate staff should be assigned to food preparation and diapering.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute diarrhea in adults".)

SUMMARY AND RECOMMENDATIONS

●Natural history – Shigella infection is usually self-limited; the average duration of symptoms associated with untreated Shigella gastroenteritis is seven days. (See 'Natural history of infection' above.)

●Antibiotic resistance – Shigella species have emerged with resistance to several antibiotics. In 2023, the United States Centers for Disease Control and Prevention (CDC) issued a health advisory regarding an increase in extensively drug-resistant (XDR) Shigella infections, defined as strains with resistance to azithromycin, ciprofloxacin, ceftriaxone, trimethoprim-sulfamethoxazole, and ampicillin. Risk groups for drug-resistant Shigella infection include men who have sex with men (MSM), people with HIV infection, people experiencing homelessness, and patients with infection acquired in Asia or Africa. (See 'Antibiotic resistance' above.)

●Supportive therapy (See 'Supportive therapy' above.)

•Hydration is important to compensate for fluid loss from the gastrointestinal tract; oral rehydration is sufficient in most cases.

•For patients with clinical features suggestive of dysentery (fever, bloody or mucoid stools), we suggest avoiding antimotility agents (Grade 2C). In such cases, antimotility agents may prolong disease or lead to more severe illness.

●Whom to treat – For adults with Shigella infection who are immunocompromised and/or have severe disease (characterized by bacteremia, intestinal or extraintestinal complications, or need for hospitalization), we recommend antibiotic therapy (Grade 1B). For other symptomatic adults with Shigella infection, we suggest antibiotic therapy (Grade 2C). We do not give antibiotics to patients with Shigella whose symptoms resolve prior to microbiologic diagnosis in the absence of antibiotic therapy.

Antibiotic treatment may shorten the duration of fever and diarrhea (by about two days) and may shorten the duration of pathogen shedding in stool, which may reduce the risk of person-to-person spread. (See 'Indications' above.)

●Antibiotic selection – For empiric treatment of patients with Shigella infection prior to availability of antimicrobial susceptibility data, antibiotic selection should be informed by the risk of drug resistance (see 'Empiric therapy' above):

•No risk for drug resistance – For patients who have no clear risk factors for drug resistance, we suggest empiric treatment with a fluoroquinolone (Grade 2C); other acceptable agents are summarized in the table (table 1).

•Patients at risk for drug-resistant infection – For patients at risk for drug-resistant infection (including MSM, international travelers, people with HIV infection and people experiencing homelessness), the clinical approach depends on the severity of illness:

-For patients who are immunocompromised and/or have severe disease (characterized by bacteremia, intestinal or extraintestinal complications, or need for hospitalization), we suggest treatment with a carbapenem (such as ertapenem, imipenem, or meropenem) (Grade 2C).

-For patients with mild to moderate illness, we suggest initial outpatient management with a fluoroquinolone (Grade 2C); in such cases, patients should be monitored carefully by telephone and the antibiotic regimen should be adjusted as needed once susceptibility results are available.

Antibiotic therapy should be tailored to antimicrobial susceptibility results when available. (See 'Directed therapy' above.)

●Follow up – Clinical improvement is expected within one to two days if Shigella infection is treated with an antibiotic to which the isolate is susceptible. If symptoms persist or worsen despite three days of treatment, repeat stool culture and susceptibility testing should be performed to evaluate for drug resistance or an alternative diagnosis. If symptoms persist despite treatment with an antibiotic to which the isolate has demonstrated in vitro susceptibility, other potential causes should be considered; pending further evaluation, switching to another antibiotic is reasonable. (See 'Follow-up' above.)

●Prevention (see 'Prevention' above)

•Patients should be counseled on practices to reduce the risk of transmission, including frequent hand washing, avoidance of food preparation for others, and safe sexual practices (table 2).

•For food handlers, healthcare workers, and childcare workers, decisions regarding follow-up testing and timing of safe return to work should be made in conjunction with guidance from local public health authorities.