Salmonella infections in the setting of AIDS: a serpentine course.

Infectious complications of the acquired immunodeficiency syndrome (AIDS) tend to be caused by organisms that fall into two broad categories: 1) opportunistic pathogens prevalent in the natural environment but rarely causing serious disease in normal hosts (Pneumocystis, Toxoplasma, Mycobacterium avium complex, Cytomegalovirus), and 2) pathogens that predictably cause disease in the general population but may be associated with atypical or highly aggressive presentations in HIV-infected patients (Pneumococcus, Mycobacterium tuberculosis, Treponema pallidum, herpes simplex virus). Since the advent of effective combination anti-retroviral therapy (ART), the incidence of systemic disease caused by opportunistic organisms has decreased substantially in the United States, and unusual presentations from the second category are probably less common as well.

The case report and clinical review by Hoag and Sessler, in this issue serves as a reminder of a sometimes forgotten entity from the second grouping: infection with enteric bacteria in the setting of advanced AIDS presenting as bacteremia and invasive disease, rather than as a self-limited diarrheal illness. Salmonellae are Gram negative, nonspore forming, and (mostly) motile bacilli which have successfully adapted to a vast array of mammalian, avian, and reptilian hosts. The long list of Salmonella varieties includes common causes of gastroenteritis worldwide. Also still common in developing countries is the more serious enteric fever, or typhoid fever, caused by the human-specific S enterica serovar Typhi and S enterica serovar Paratyphi A and B. Twenty-five years ago, numerous human pathogen Salmonella species were named, but in the age of molecular medicine, taxonomy has attempted to relegate all Salmonella into a single species (Salmonella enterica). The old species names and lettered serogroups (A, B, C, D) are still used to describe serovarieties of S enterica, as well as to spell out the older names in deference to clinical and literary tradition. The agents of enteric fever are typically spread directly from person to person. Non-Typhi Salmonellae can be spread to humans by direct contact with animals (such as domesticated birds, pet snakes, and amphibians) or by ingesting undercooked or raw animal products, plant foods contaminated by animal waste (inadequately washed berries, produce, or herbs), and other foods cross-contaminated on cutting boards. S enterica subspecies arizonae, the organism isolated from the patient described in this issue, is a so-called "nongroupable" subspecies and is less closely related to other non-Typhi human pathogens. This organism has been linked to contact with reptiles and specifically, the use of rattlesnake meat for medicinal purposes by some Latin Americans and Native Americans. (1-2) The desiccated rattles of infected snakes, when dispensed as folk remedies, are capable of spreading disease when ingested. The woman described in the current case report denied any contact with reptiles; although she raised chickens, there is no evidence this was related to the S enterica subspecies arizonae isolates.

Salmonella infections were recognized as important HIV complications early on in the AIDS epidemic. (3-5) While HIV-infected patients have been estimated to be up to 60 times more susceptible to non-Typhi Salmonella infections than the general population, (6) perhaps even more clinically striking is the greatly increased risk of bacteremia, metastatic abscesses, and fulminant sepsis presentations in addition to, or in place of, the usual gastroenteritis symptoms. In some cases these infections are refractory to appropriately chosen antibacterial therapy. The majority of AIDS-related Salmonella cases in some series involve bacteremia, compared with a much smaller proportion of cases among immunocompetent adults. (7) While antibiotics are not always necessary for nonbacteremic salmonellosis in normal hosts, fluoroquinolone therapy (typically ciprofloxacin 500-750 mg orally twice daily) is strongly recommended in the AIDS setting.

Even when patients with AIDS had a successful response to initial antibacterial therapy for salmonellosis in the pre-ART era, frequent relapses were common (nearly half of all cases in some reports). Prolonged fluoroquinolone therapy is often recommended in the setting of advanced immunosuppression to suppress relapses. (8) The reasons for these relapses are not fully understood, but long-term colonization has been documented in the biliary system, and in some cases, cholecystectomy has been pursued as an attempt at cure. In the non-HIV clinical setting, older patients with vascular disease, particularly aortic aneurysms and vascular prosthetic implants, have been known to be at risk for mycotic aneurysms, endocarditis and disseminated infections complicating Salmonella bacteremia; (9) such a possibility should not be overlooked in AIDS patients. While the patient described in the accompanying case report developed bloody pericardial effusion during the course of sepsis, this occurred after the infusion of anticoagulants and should not be considered as proof of invasive pericardial infection. It is evident, however, that this organism has an affinity for vascular and mesenteric tissues in the right clinical settings.

It is likely that relapsing or persistent salmonellosis will be less frequently encountered when affected patients have successfully responded to ART. One interesting sidebar is that the first approved antiretroviral agent, zidovudine, also has anti-Salmonella activity and documented in vitro synergy with conventional antibacterial agents against this pathogen. (10) While many factors must be considered in choosing the optimal antiretroviral regimen for each individual, it might be reasonable to incorporate zidovudine into the treatment plan for this patient, if convenient and otherwise indicated, for a rare opportunity to take aim at "two birds" with "one stone."

References

1. Waterman SH, Juarez G, Carr SJ, et al. Salmonella arizonae infections in Latinos associated with rattlesnake folk medicine. Am J Public Health 1990;80:286-289.

2. Bhatt BD, Zuckerman MJ, Foland JA, et al. Disseminated Salmonella arizona infection associated with rattlesnake meat ingestion. Am J Gastroenterol 1989;84:422-425.

3. Gruenewald R, Blum S, Chan J. Relationship between human immunodeficiency virus infection and salmonellosis in 20- to 59-year-old residents of New York City. Clin Infect Dis 1994;18:358-63.

4. Celum CL, Chaisson RE, Rutherford GW, et al. Incidence of salmonellosis in patients with AIDS. J Infect Dis 1987;156:998-1002.

5. Sperber SJ, Schleupner CJ. Salmonellosis during infection with human immunodeficiency virus. Rev Infect Dis 1987;9:925-934.

6. Gotuzzo E, Frisancho O, Sanchez J, et al. Association between the acquired immunodeficiency syndrome and infection with Salmonella typhi or Salmonella paratyphi in an endemic typhoid area. Arch Intern Med 1991;151:381-382.

7. Goldberg MB, Rubin RH. The spectrum of Salmonella infection. Infect Dis Clin North Am 1988;2:571-598.

8. Jacobson MA, Hahn SM, Gerberding JL, et al. Ciprofloxacin for Salmonella bacteremia in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1989;110:1027-1029.

9. Fernandez Guerrero ML, Aguado JM, Arribas A, et al. The spectrum of cardiovascular infections due to Salmonella enterica: a review of clinical features and factors determining outcome. Medicine 2004;83:123-138.

10. Lewin CS, Allen RA, Amyes SG. Antibacterial activity of fluoroquinolones in combination with zidovudine. J Med Microbiol 1990;33:127-131.

Mistakes are the portals of discovery.
--James Joyce

J. Michael Kilby, MD

From the University of Alabama at Birmingham, Birmingham, AL.

Reprint requests to Dr. J. Michael Kilby, UAB 1917 Clinic, 908 20th Street South, University of Alabama at Birmingham, Birmingham, AL, 35294-2050. Email: [e-mail]

Accepted April 20, 2005.