Persistence of Salmonellae in Blood and Bone Marrow: Randomized Controlled Trial Comparing Ciprofloxacin and Chloramphenicol Treatments against Enteric Fever

Abstract

We performed a randomized controlled trial involving 55 adult patients with enteric fever to compare ciprofloxacin and chloramphenicol. Blood and bone marrow cultures and cytokine profiles during therapy were done to compare the clinical and bacteriological efficacies of these drugs. All patients were randomly assigned to receive chloramphenicol (500 mg four times a day orally) for 14 days or ciprofloxacin (500 mg twice a day orally) for 7 days. In each treatment group, patients were subsequently randomized to have blood and bone marrow cultured after either 3 or 5 days of treatment. Twenty-seven patients received chloramphenicol, and 28 received ciprofloxacin. The two groups were similar in terms of baseline characteristics. No significant differences in clinical cure and time to defervescence were found. All strains isolated were susceptible to both antibiotics. Although ciprofloxacin was more effective in the elimination of Salmonella enterica serovars Typhi and Paratyphi A from bone marrow than chloramphenicol, there was still an impressive persistence of Salmonella in the bone marrow culture (67%). In the ciprofloxacin-treated patients the suppressed cytokine production capacity showed a trend to normalize earlier than in patients treated with chloramphenicol.

Survival ofSalmonella entericaSerovar Typhimurium within Late Endosomal-Lysosomal Compartments of B Lymphocytes Is Associated with the Inability To Use the Vacuolar Alternative Major Histocompatibility Complex Class I Antigen-Processing Pathway

“…It would be interesting to define whether B lymphocytes mediate Salmonella transit from intestinal wall to spleen, liver, or bone marrow, the main targets for Salmonella persistence (13,20,26,56). In fact, it has been demonstrated that activated B lymphocytes travel from lymphoid organs to bone marrow to become antibody-producing cells.…”

Epidemiology, Clinical Presentation, Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella Infections

“…The succinate ester prodrug is used for intravenous or intramuscular administration and gives lower serum levels than the oral form (436,437). Chloramphenicol has been shown to be clinically effective in a number of studies (341,(438)(439)(440)(441)(442)(443)(444)(445)(446)(447). Disadvantages of chloramphenicol are its four-times-daily administration and the need to give it for at least 2 weeks to reduce the 10 to 15% risk of relapse.…”

Organic Anion Transporter 3 (Oat3/Slc22a8) Interacts with Carboxyfluoroquinolones, and Deletion Increases Systemic Exposure to Ciprofloxacin

“…Ciprofloxacin is a broad-spectrum antimicrobial that is used in the treatment of numerous infectious diseases, including those afflicting the skin (Lipsky et al, 1999), bone (Gasem et al, 2003), gastrointestinal tract (Hsieh et al, 1998), genitourinary system (Wagenlehner et al, 2006), lungs (Jones, 2002), and meninges (Gogos et al, 1991). It is also a preferred agent for the prevention and treatment of anthrax (Meyerhoff et al, 2004).…”