Medical Care
Salmonella gastroenteritis is usually a self-limiting disease. Fluid and electrolyte replacement may be indicated in severe cases. Because antibiotics do not appear to shorten the duration of symptoms and may actually prolong the duration of convalescent carriage, they are not routinely used to treat uncomplicated nontyphoidal Salmonella gastroenteritis. Current recommendations are that antibiotics should be reserved for patients with severe disease or patients who are at a high risk for invasive disease.
Historically, recommended regimens for the treatment of typhoid fever included ampicillin, trimethoprim-sulfamethoxazole, or chloramphenicol. Emerging drug resistance over the past 20 years has limited the usefulness of these antibiotics. Presently, quinolone, macrolide, and third-generation cephalosporin antibiotics are preferred for empiric therapy pending sensitivities. Unfortunately, sensitivity to quinolones has been steadily declining, and these are no longer fool-proof agents for typhoid fever. A growing rate of resistance of nontyphoidal salmonella to nalidixic acid and ceftriaxone has been reported. [46]
Clinical data suggested reduced effectiveness of quinolone therapy in patients with nalidixic acid-resistant Salmonella strains. [47] A study of more than 1000 stored Salmonella isolates from Finland has confirmed earlier data that showed that resistance to nalidixic acid by means of disk diffusion is a sensitive and specific method of screening Salmonella isolates for reduced susceptibility to fluoroquinolones. [48]
Although uncommon in the United States, resistance to quinolone antibiotics among typhoidal and nontyphoidal salmonellae is increasingly common elsewhere. In one 22-year surveillance study in Spain, the prevalence of nalidixic acid resistance increased almost 80-fold to 38.5%.
In a review of US data from the National Antimicrobial Resistance Monitoring System, 58% of S typhimurium isolates isolated between 1997 and 1998 were resistant to at least one antibiotic, and 3 multidrug-resistant strains (resistant to ≥5 antibiotics) accounted for 74% of isolates.
The decline in prevalence of chloramphenicol resistance in many endemic areas has led to reconsideration of its use as an alternative to newer-generation fluoroquinolones or azithromycin.
There are widespread concerns about aplastic anemia with chloramphenicol and dysglycemia with gatifloxacin. In most developed settings, there also are cautions or specific constraints about the use of fluoroquinolones in children and pregnant or nursing mothers, because of potential cartilage toxicities; other adverse effects such as photosensitivity, electrocardiographic abnormalities, and tendinopathies largely affect elderly patients with concomitant problems such as renal impairment. [49]
Azithromycin is likely to be the preferred empirical treatment, often given together with ceftriaxone, in developed countries where chloramphenicol is usually reserved for life-threatening situations, for which no alternatives are available, and physicians are reluctant to use fluoroquinolones in children and lack easy access to gatifloxacin. [49]
In an endemic area such as Nepal, gatifloxacin is as effective as chloramphenicol in ambulatory young patients, and adherence to treatment is improved by the shorter duration and smaller number of tablets in the gatifloxacin regimen. [49]
Salmonella bacteremia is generally treated with a single bactericidal drug for 10-14 days. Given the resistance trends, life-threatening infections should be treated with both a third-generation cephalosporin and a fluoroquinolone until the susceptibilities of antimicrobial agents are known. [2]
If endocarditis or infectious arteritis is documented, urgent surgical treatment is usually necessary. Antimicrobial therapy for endovascular infections should be continued for a minimum of 6 weeks after successful surgery.
Years of therapy might be needed when surgery is not possible (eg, retained prosthetic devices, chronic bone and joint infections). [2]
For proven or possible CNS involvement, high-dose ceftriaxone would be the best choice for optimal penetration of the blood-brain barrier. [2]
Treatment of salmonella infection in pregnancy is controversial, and antibiotic therapy should be reserved for cases of invasive disease, using amoxicillin or cephalosporin. [50] Case reports describe of fetal loss in the setting of disseminated Salmonella infection. [51, 50]
Surgical Care
Typhoid fever is occasionally complicated by intestinal perforation or hemorrhage, cholecystitis, endocarditis, arteritis, osteomyelitis, or soft-tissue abscess formation, necessitating surgical intervention.
Long-term S typhi carriage (usually with the gallbladder as the reservoir) may necessitate cholecystectomy.
Splenectomy may be required for splenic abscesses. [2]
Surgical care dramatically improves the likelihood of survival in patients with endarteritis, especially that which involves abdominal aorta. A review of 148 cases from 1948-1999 found a 62% survival rate in all patients treated with combined surgical and medical therapy and a 77% survival rate in 30 patients who were able to undergo extra-abdominal bypass with construction of an axillobifemoral graft. [52, 53]
Consultations
Consultation with an infectious disease specialist should sought in cases of bacteremia, endovascular infections, CNS infections, and whenever typhoid fever is a strong possibility, as well as when antimicrobial resistance is suspected or documented.
Prevention
Currently, two typhoid vaccines are internationally and commercially available, and both have been shown to be safe and efficacious. [54]
The first is an oral vaccine based on a live attenuated S typhi Ty21a strain (Vivotif), which has been developed in two formulations: enteric coated capsules and a liquid formulation. Revaccination with Vivotif is recommended every 5 years. The second is a Vi capsular polysaccharide (Typhium Vi) vaccine, which is injectable. Revaccination with Typhium Vi is advised every 2 years. [55] Both vaccines are moderately effective, with a cumulative efficacy of approximately 70%. Protection may be much poorer in individuals who are frequently exposed to high inocula of S typhi. Neither of the above vaccines are available for children younger than 2 years.
The new and unlicensed modified conjugated Vi vaccine (Vi-rEPA) is based on Vi conjugated to rEPA, a recombinant exoprotein A from Pseudomonas aeruginosa. Vi-rEPA is equally efficacious and may confer longer immunity. [56] In 2013, two Vi-tetanus toxoid conjugates were licensed in India for persons aged 3 months or older. This new generation of typhoid vaccine opens up a new era of typhoid prevention and elimination. [56]
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Rose spots on abdomen of a patient with typhoid fever due to the bacterium Salmonella typhi. Courtesy of CDC/Armed Forces Institute of Pathology, Charles N. Farmer.
