Typhoid Fever Pharmacotherapy

Typhoid Fever Pharmacotherapy

1. Definition, causative organisms & clinical context

• Enteric (typhoid) fever is a systemic febrile illness caused by the human-restricted invasive serovars of Salmonella enterica subspecies enterica: Salmonella Typhi (typhoid fever) and Salmonella Paratyphi A, B, C (paratyphoid fever); together these constitute enteric fever, distinct from the self-limiting gastroenteritis of nontyphoidal Salmonella (NTS). (G&G 14e Ch.57, p.1143 — enteric fever caused by Salmonella typhi)
• The organism is a facultative intracellular Gram-negative bacillus; disease reflects bacteraemic dissemination and reticuloendothelial (macrophage) survival, explaining why effective drugs must achieve good intracellular and biliary concentrations, not merely luminal gut levels. (G&G 14e Ch.57, p.1142 — several intracellular bacteria inhibited by fluoroquinolones at plasma-achievable concentrations)
• Antimicrobial therapy is almost always empirical at initiation — the causative organism and susceptibility are not known for 24–48 h (blood-culture turnaround) — and enteric fever is precisely the "high-risk if treatment delayed" syndrome for which G&G endorses starting empirical therapy on likely syndrome + local epidemiology (prevalence of drug-resistant organisms) + patient risk factors. (G&G 14e Ch.56, p.1129 — empiric therapy rationale)
• Definitive therapy is selected once culture + susceptibility return; the enteric-fever principle of de-escalation/streamlining to the narrowest effective agent applies, and monotherapy is preferred for a defined pathogen unless combination is specifically justified. (G&G 14e Ch.56, p.1129 — definitive therapy, streamlining, monotherapy default)
• The chronic-carrier state — persistent gallbladder/biliary carriage of S. Typhi with faecal shedding — is a distinct pharmacotherapeutic target (eradication of biliary reservoir), separate from acute-illness cure. (G&G 14e Ch.57, p.1143 — fluoroquinolones "clear chronic fecal carriage")