What are the guidelines for managing Enteric fever in adults and pediatric patients?

Management of Enteric Fever

Immediate Empiric Antibiotic Therapy

Patients with clinical features of sepsis who are suspected of having enteric fever should be treated empirically with broad-spectrum antimicrobial therapy immediately after blood, stool, and urine culture collection. 1

• Antibiotic therapy should begin within 1 hour after the diagnosis of sepsis is considered, as delay of effective antimicrobial therapy has been associated with increased mortality from infection and sepsis. 1
• Early treatment in the clinical course results in better outcomes than delayed treatment, with lower case fatality ratios and shorter time to fever resolution. 1

First-Line Antibiotic Selection

For Adults

Ceftriaxone is the preferred first-line agent for enteric fever in adults, particularly given widespread fluoroquinolone resistance. 2

• Ceftriaxone 2-4 grams IV daily is the recommended regimen based on current resistance patterns. 3, 2
• Azithromycin (500 mg daily for 7 days or 1 gram single dose) is an alternative first-line option with excellent susceptibility (97%). 3, 2
• Fluoroquinolones should be avoided as empiric therapy due to widespread resistance, particularly in South Asia where ciprofloxacin-susceptible strains are detected in only 12% of cases. 3

For Pediatric Patients

Third-generation cephalosporins (ceftriaxone) are the preferred first-line treatment for children with enteric fever. 1, 2

• Ceftriaxone 50-75 mg/kg/day IV (maximum 2-4 grams daily) is the standard pediatric regimen. 2, 4
• Azithromycin is an alternative option depending on local susceptibility patterns. 1
• Ceftriaxone may result in decreased clinical failure compared to azithromycin in pediatric patients. 2

Treatment Duration and Monitoring

Continue ceftriaxone for at least 4 days after defervescence to prevent relapse. 3

• The overall relapse rate with ceftriaxone monotherapy is approximately 11%, with longer times to treatment initiation and defervescence (>7 days) being risk factors for relapse. 3
• If defervescence takes longer than 7 days, consider switching to a fluoroquinolone if the strain is found to be susceptible. 3
• Time to defervescence with ceftriaxone may be shorter (approximately 0.5 days) compared to azithromycin. 2

Narrowing Antimicrobial Therapy

Antimicrobial therapy should be narrowed when antimicrobial susceptibility testing results become available. 1

• If an isolate is unavailable and there is clinical suspicion of enteric fever, antimicrobial choice may be tailored to susceptibility patterns from the setting where acquisition occurred. 1
• Isolates show excellent susceptibility to ampicillin (91%), chloramphenicol (94%), ceftriaxone (97%), and azithromycin (97%), suggesting these older agents may be reconsidered as treatment options in Asia. 3

Alternative Regimens Based on Susceptibility

When Fluoroquinolone Susceptibility is Confirmed

• Ciprofloxacin 500-750 mg twice daily for 7-10 days can be used if the strain is susceptible. 5, 2
• However, fluoroquinolone resistance often precludes the use of ciprofloxacin in South Asia. 2

For Extensively Drug-Resistant (XDR) Strains

• Since 2016, there has been an ongoing outbreak of XDR enteric fever in Pakistan that only responds to a limited number of antibiotics. 6
• Azithromycin and carbapenems may be the only effective options for XDR strains. 6, 7

Management of Complications

Enteric fever can cause life-threatening complications requiring intensive care management. 4

• Complications include intestinal perforation, encephalopathy, myocardial dysfunction, bleeding, bone infections, and secondary hemophagocytic lymphohistiocytosis. 6, 4
• Patients with complications may require vasoactive drugs, mechanical ventilation, dexamethasone, and intravenous immunoglobulin in addition to antibiotics. 4
• Intestinal perforation and death were more common in the preantibiotic era, emphasizing the importance of early antibiotic treatment. 1

Management of Chronic Carriers

Some patients may continue to carry the bacteria in their stool for a long time following treatment and may need a longer course of antibiotics to eradicate infection. 6

• Follow-up stool testing may be required by local health authorities following cessation of diarrhea to enable return to child care, employment, or group social activities. 1
• Practitioners should collaborate with local public health authorities to adhere to policies regarding return to settings where transmission is a consideration. 1

Supportive Care

Aggressive rehydration is essential as adjunctive therapy to antibiotics. 1

• Use reduced osmolarity oral rehydration solution (ORS) for mild to moderate dehydration. 5, 8
• Intravenous fluids are indicated for severe dehydration, shock, altered mental status, or ileus. 5
• Reassessment of fluid and electrolyte balance and nutritional status is recommended in patients with persistent symptoms. 1, 8

Critical Pitfalls to Avoid

• Never delay antibiotic therapy while awaiting culture results in patients with suspected enteric fever and sepsis. 1
• Do not use fluoroquinolones empirically without considering local resistance patterns, as resistance exceeds 90% in many endemic regions. 3, 2
• Avoid treating asymptomatic contacts, as they should not be offered empiric treatment but should follow appropriate infection prevention and control measures. 1, 8
• Do not discontinue antibiotics prematurely, as treatment should continue for at least 4 days after defervescence to prevent relapse. 3

Prevention Strategies

• Travelers can reduce their risk of acquiring enteric fever by following safe food and water practices and receiving vaccination at least a few weeks before travel. 6
• Improvement of sanitation, promotion of food hygiene, and detection and control of chronic carriers are essential preventive control measures. 7