Pathogens>Bacteria>

MICROBIOLOGY

• Facultatively anaerobic, gram-negative bacillus, foodborne (95% cases: outbreaks linked to multiple vehicles including eggs, poultry, meats, dairy or vegetables) or zoonotic pathogen, except S. typhi (typhoid fever) and S. paratyphi (paratyphoid fever), which colonize/infect humans only.
• Non-typhoidal strains classified by agglutination reactions to O antigens identifying serogroups A-E; approximately 2,500 serovars/serotypes exist. Most common in US are S.  Typhimurium, S. Enteriditis, S. Newport. S. enterica or S. choleraesuis sometimes used as single name for clinically familiar serovars (e.g., S. enterica Typhimurium).
• Typhoidal species S. typhi (serogroup D) and S. paratyphi more difficult to Cx. Increased yield when blood, bone marrow and intestinal secretions Cx'd before or soon after ABx initiated
• Recovery of organism possible from almost any site, but most commonly stool followed by blood
• Grows on standard media for stool; fresh stool specimen preferred; rectal swabs inferior

CLINICAL

• Nontyphoidal Salmonella gastroenteritis: nausea, vomiting, diarrhea +/- fever, bloody stools (only ~50% of the time)usually occur within 6-72 hrs of ingestion of contaminated food or water; usually self-limited lasting 3-7 d. Occasionally more prolonged illness with fever, bloody diarrhea, weight loss. Mean carriage after resolution of Sx up to 4-5 wks and varies by serotype. Salmonella cannot be reliably be distinguished from other common enteric pathogens on a clinical basis.
• Extraintestinal salmonellosis: almost any site can be involved;clinical disease depends on site (see Sites of Infection). Bacteremia usually occurs with advanced immunosuppression. Approximately 5-10% develop localized infection after bacteremia.
• HIV+ pts at 20-100-fold increased risk of salmonellosis than general population, and more likely to have invasive disease including recurrent bacteremia.
• Patients with AIDS and Salmonella bacteremia at risk for relapse, recurrence when not on HAART
• Typhoid fever (S. typhi) rarely reported with HIV even in developing world; rare in US but consider in returning traveler, particularly from India, other Asian countries, South America, and Africa. Sx initially nonspecific but then may develop fever, abdominal pain, +/- diarrhea, neuropsychiatric 10-15%, rose spots 15-30%, hepatomegaly 50%. Lasts up to 4 wks without ABx and complications can occur. Paratyphoid illness similar but usually less severe.

SITES OF INFECTION

• GI tract: gastroenteritis, enteric fever (acute fever, abdominal tenderness +/- diarrhea and nonspecific Sx mostly due to S. typhi and S. paratyphi), rectal ulcers
• Bacteremia: AIDS increases risk; recurrent nontyphoidal bacteremia is AIDS-defining illness
• Extraintestinal sites (rare): endocarditis, aortitis/arteritis, lung abscess, osteomyelitis, meningitis and brain abscess, parotitis, liver abscess, UTI, septic and reactive arthritis, genital abscess, soft tissue infections
• Carriage: Transient, asymptomatic carrier state can occur with median duration of excretion in stool of 3-4 wks. Chronic carrier state:persistence of Salmonella in stool or urine for >1 yr. Biliary tree (gallbladder) major nidus. Occurs in <1% with nontyphoid and 1-4% with typhoid strains. Antimicrobials can increase persistence of transient carriage but often used to treat chronic carriage.

TREATMENT

• HIV-infected persons at increased risk for invasive, recurrent, and most notably drug-resistance
• If deciding to treat, choice usually empiric, so choice often guided by desire to cover common enteric pathogens.
• Immunocompetent patients without HIV often do not require treatment; condition self-limited and ABx may prolong carrier state (IDSA Guidelines CID 2001;32:331). Most experts recommend treatment in HIV population, though no data from clinical trials support this recommendation.
• Treatment duration not well defined: 7-14 d for mild, nonbacteremic cases with CD4 >200; >4-6 wks for AIDS, CD4 <200, or bacteremic cases
• Fluid and electrolyte replacement important
• If susceptibilities unknown, use PO fluoroquinolone, azithromycin, or TMP-SMX initially, then modify Rx according to susceptibilities when available. Ampicillin and TMP-SMX resistance now more common (see Treatment Regimens and Doses).
• Fluoroquinolones, 3rd generation cephalosporins and azithromycin effective for S. typhi and S. paratyphi.

• Hospitalized pts or pts with severe diarrhea (>5 stools/d and/or T >101^oF, tenesemus, blood or fecal leukocytes), bacteremia or extraintestinal infections such as meningitis, lung abscess, osteomyelitis should be empirically treated with PO or IV fluoroquinolones. Alternatives include azithromycin or IV/IM 3rd generation cephalosporin such as ceftriaxone. Narrow treatment once susceptibilities known.
• Fluid and electrolyte replacement important
• Possible or confirmed S. typhi infection:ciprofloxacin or ceftriaxone x 10-14 days. Alternatively azithromycin 1 gm PO x 1 then 500 mg PO qd x 6 d. If associated with shock, consider dexamethasone a few minutes before antibiotic: 3 mg/kg then 1 mg/kg q6h x 8 doses (NEJM 310:82,1984 : mortality benefit but study did not include HIV patients) Consider ID consultation.

• Ciprofloxacin: PREFERRED agent: 500 mg PO bid for gastroenteritis; 750 mg PO BID if bacteremia; 400 mg IV bid if unable to take oral medications or concern about poor absorption. Can also use ofloxacin 400 mg PO bid or norfloxacin 400 mg PO bid.
• Little to no data for other fluoroquinolones but likely to be effective. Levofloxacin 500 mg PO or IV qd;  moxifloxacin 400 mg PO or IV qd
• TMP/SMX: Effective, but resistance reported. 1 DS P) bid
• Ceftriaxone: Effective for both nontyphoidal and typhoidal salmonellosis. 1-2 gm IV or IM qd. Cefotaxime 1-2 gm IV q8h also effective.
• Azithromycin: Effective alternative for both nontyphoidal and typhoidal salmonellosis, particularly in patients with multiple allergies or pregnant patients. 500 mg PO qd.
• Aztreonam: Alternative in patients with multiple allergies based on in vitro data. 1-2 gm IV q8h

Drug Comments

FOLLOW UP

• Causes of treatment failure: resistance, malabsorption of PO ABx, sequestered focus of infection, or drug interactions.
• Monitor response to Rx, esp. in pts w/ advanced HIV+ infection. F/U stool Cx to demonstrate cure not required except with clinical failure or for public health reasons (e.g. food service or health care worker).
• Transient, asymptomatic carrier state can occur with median duration of excretion in stool of 3-4 wks. Chronic carrier state refers to persistence in stool or urine for >1 yr. Biliary tree (gallbladder) is major nidus. Occurs in <1% with nontyphoid and 1-4% with typhoid strains.
• ABx can increase persistence of transient carriage but often used to treat chronic carrier state. Ceftriaxone or fluoroquinolones preferred. If biliary disease present, best results with cholecystectomy and 10-14d ABx course initiated before surgery.

OTHER INFORMATION

• AZT has documented anti-Salmonella activity in vitro, and appears to be clinically useful in prevention of relapse
• Prevention: 1) handwashing with soap/hand sanitizers after handling of raw meats, eggs, poultry; 2) cook meats, poultry thoroughly; 3) wash fresh produce
• Useful websites: http://www.cdc.gov/foodnet//and http://www.cdc.gov/narms/ (CDC's foodborne diseases websites); http://www.idsociety.org/ (select practice guidelines for HIV/AIDS)
• Report salmonellosis to local and/or state public health authorities

REFERENCES

REFERENCED WITHIN THIS GUIDE

• Amoxycillin
• Ampicillin
• Ciprofloxacin
• Lymphoid interstitial pneumonitis