Campylobacter species are among the most common pathogens in humans and are commensal in birds, swine, and cattle. It is the most common cause of culture-proven bacterial gastroenteritis in developed and developing countries, responsible for 400 million–500 million cases of diarrhea each year. In the United States, >1% of the population acquires the infection each year. Although diarrhea is the most frequent clinical manifestation of Campylobacter species infection, a broad clinical spectrum is associated with this infection, from asymptomatic carriage to systemic illness and bacteremia to localized infection and association with Guillain-Barré syndrome, a severe immunoreactive complication.

In the United States, an estimated 2 million cases of campylobacteriosis occur each year. It is the most common bacterial cause of foodborne illness [1]. The overall incidence of laboratory-confirmed Campylobacter infection in 2005 in the United States was 12.7 cases per 100,000 population, representing a 30% decrease since 1996 [2]. However, the incidence of symptomatic Campylobacter species infection has been estimated at 760–1100 cases per 100,000 population [3]. Age-specific rates of Campylobacter jejuni isolation in patients with diarrhea differ among countries. In industrialized countries, C. jejuni is isolated from 5%–16% of children with diarrhea, with a prevalence of infection in healthy children of 0%–1.5% [1]. In children <5 years of age, the incidence of laboratory-confirmed Campylobacter species infection is 43.4 cases per 100,000 person-years (up to 54.3 cases per 100,000 person-years in children <1 year of age), and the associated male-female ratio is 1.34 : 1 [4]. It is the third most common cause of hospitalization for gastroenteritis after rotavirus and Salmonella species infection, with a hospitalization rate of 10.8% for all Campylobacter species infections [5–7]. Studies of the disease burden of Campylobacter species infection in The Netherlands have estimated that intestinal infection in general accounts for 67,000 disability-adjusted life years per year and that Campylobacter species infections represent at least one-third of the disease burden of all intestinal infections [8]. The cost per case of gastrointestinal infection in Europe has been estimated to be US$94–US$132. In England, the total cost of gastrointestinal infections was estimated to be US$1.23 billion each year. Of this amount, US$116 million is spent on cases of Campylobacter species infection, the highest cost associated with a particular pathogen (including rotavirus and Salmonella) [9].

Campylobacter species infection is generally associated with mild illness and only occasionally is fatal [10]. The mortality rate associated with symptomatic Campylobacter species infection has been estimated at 24 deaths per 10,000 culture-confirmed cases, or 200 deaths per year in the United States [3].

In areas of endemicity in developing countries, the isolation rate in children with diarrhea is 8%–45%, with a similar rate of isolation in asymptomatic children [11–14]. Infections occur early in life, with the highest proportion of C. jejuni isolates obtained from children <5 years of age [12–14]. The annual incidence of Campylobacter species infections can be as high as 2.1 episodes per child. Infections acquired early in life are more likely to be associated with diarrhea, whereas those occurring beyond the age of 4 years, although relatively common, are mostly asymptomatic [12].

Rehydration and correction of electrolyte abnormalities are the mainstay of treatment of patients with Campylobacter species enteritis. Debate exists over the need to administer antimicrobial agents in uncomplicated infections. Antibiotic treatment should be considered for C. jejuni–infected patients who have bloody diarrhea, fever, worsening of symptoms, or a large number of stools, or in those who are immunosuppressed. Campylobacter species are often resistant to penicillin, ampicillin, and cephalosporins, as a result of an alarming increase in fluoroquinolone resistance in the past decade in most countries [15]. This increase in fluoroquinolone resistance coincides with the recent licensure of fluoroquinolones (sarafloxacin and enrofloxacin) for use in poultry and in veterinary medicine in general, which has increased the reservoir of resistant Campylobacter species [16]. Most strains of C. jejuni and Campylobacter coli are susceptible to erythromycin, azithromycin, gentamicin, tetracycline, and chloramphenicol [17]. When antibiotic therapy is indicated, erythromycin is the drug of choice and is administered for 5–7 days [18]. Campylobacter species have little propensity to select for plasmid-mediated resistance to erythromycin, although resistance to this antibiotic has been reported in many countries where it is used indiscriminately [19]. Studies have shown no clinical benefit of erythromycin therapy versus placebo if administered late in the course of illness. Shedding of the organism can persist for 2 weeks to 3 months in immunocompetent hosts who are not treated with antibiotics. Furazolidone or azithromycin may be useful in the treatment of C. jejuni infections of the gastrointestinal tract. In severe sepsis, parenteral antibiotics are necessary. Although it is rarely associated with mortality, Campylobacter infection is an important public health concern as a consequence of its high incidence, its frequent association with severe diarrhea, and the occurrence of extraintestinal complications, such as Guillain-Barré syndrome. Thus, treatment of this infection is justified on this basis. However, several observations lead to questioning of the beneficial effects of antibiotics. First, a significant clinical effect is only observed when treatment is established early during the course of illness, as suggested by the meta-analysis study by Ternhag et al. [21], published in this issue of Clinical Infectious Diseases. Second, no information is available on the outcome of the use of effective treatment to prevent extraintestinal immunoreactive complications. Third, there has recently been an alarming emergence of drug resistant strains, especially fluoroquinolone-resistant strains, as a consequence of antibiotic misuse in veterinary medicine. Several studies have shown that patients infected with a quinolone- or erythromycin-resistant strain of Campylobacter species have an increased risk of an adverse event, compared with patients infected with quinolone- and erythromycin-susceptible Campylobacter species strains, and that infection with quinolone- or erythromycin-resistant Campylobacter species strains causes a longer duration of illness [19, 20].

There are very few randomized studies that compare antibiotics with placebo for the treatment of Campylobacter species–related diarrhea. Some of these studies show that antibiotics have no effect; therefore, the meta-analysis study by Ternhag et al. [21], which includes all relative published trials, is justified. This analysis clearly shows a significant decrease in symptoms and bacterial shedding time; further, although not significant, a trend was observed for a beneficial effect of antibiotics only when early treatment was started. When analyzing individual studies, this effect is more evident for severe diarrhea, dysentery-related diarrhea, and diarrhea in more-susceptible individuals and in travelers. Therefore, to be effective, antimicrobial treatment should be initiated early in the course of illness and should include active antibiotics. Unfortunately, the high resistance of this organism to quinolones and the rapid emergence of erythromycin-resistant strains limit the available options, leaving the problem of treatment of Campylobacter species infections unresolved. Thus, prevention and control programs become relevant and should focus on (1) banning the use of antibiotics as growth promoters in poultry farms at the international level, especially in countries with emerging economies where antibiotic use is unrestricted; (2) universal implementation of control systems to prevent transmission of Campylobacter species in intensive poultry industries; and (3) the promotion of health education in populations at risk. The research on new anti-infective agents that appear to avoid the drug resistance, such as agents that use synthetic receptor analogue oligosaccharides and glycoconjugates, as well as pre- and probiotics, is warranted [22].

## Acknowledgments

Potential conflicts of interest. G.M.R-P.: no conflicts.

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