What is the clinical significance and recommended treatment of Prevotella jejuni isolated from a specimen (e.g., jejunal biopsy in a child with celiac disease or from a normally sterile site)?

Prevotella jejuni: Clinical Significance and Management

Clinical Significance

Prevotella jejuni is a novel anaerobic gram-negative bacterium first isolated from the jejunal mucosa of a child with celiac disease, but its pathogenic role remains unclear and it should be considered a potential opportunistic pathogen when isolated from normally sterile sites. 1

Microbiological Characteristics

• P. jejuni is an obligately anaerobic, gram-negative, non-spore-forming bacillus that appears as short rods or coccoid cells, occasionally forming longer filamentous structures. 1
• The organism is both saccharolytic and proteolytic, producing acetic acid and succinic acid as major metabolic end products. 1
• P. jejuni demonstrates unique adhesive properties, forming homologous aggregates with tube-like structures connecting individual bacterial cells and binding to human intestinal carcinoma cell lines at 37°C. 1
• Phylogenetically, P. jejuni is most closely related to but distinct from Prevotella melaninogenica, based on 16S rRNA, rpoB, and cpn60 gene sequencing. 1

Clinical Context and Interpretation

• The isolation of P. jejuni from a jejunal biopsy in a child with celiac disease does not establish causation—it may represent part of the altered intestinal microbiota associated with celiac disease rather than a primary pathogen. 1
• When P. jejuni is isolated from normally sterile sites (blood, abscess fluid, deep tissue), it should be treated as a clinically significant pathogen requiring antimicrobial therapy. 1, 2
• The organism's ability to adhere to intestinal epithelial cells suggests potential for mucosal colonization and possible opportunistic infection in immunocompromised hosts or patients with disrupted mucosal barriers. 1

Antimicrobial Susceptibility and Treatment Recommendations

First-Line Empiric Therapy

For confirmed infections with Prevotella species (including P. jejuni), piperacillin-tazobactam, cefoxitin, or tigecycline should be used as first-line empiric therapy based on their excellent in vitro activity against Prevotella species. 3

• Piperacillin-tazobactam demonstrates 100% susceptibility against Prevotella species in recent surveillance data from Turkey. 3
• Cefoxitin shows universal susceptibility (100%) and represents an excellent alternative for empiric coverage. 3
• Tigecycline maintains complete activity (100% susceptibility) against all tested Prevotella isolates. 3

Carbapenem Therapy

• Imipenem and meropenem both demonstrate 100% susceptibility against Prevotella species but should be reserved for serious mixed infections or when other resistant organisms are suspected. 3
• Carbapenems should not be used as first-line agents for isolated Prevotella infections to preserve their utility for multidrug-resistant pathogens. 3

Antimicrobials to Avoid Without Susceptibility Testing

• Ampicillin monotherapy should be avoided, with resistance rates of 57.6% documented in Prevotella species. 3
• Clindamycin shows concerning resistance rates of 36.4% and should not be used empirically without susceptibility confirmation. 3
• Tetracycline resistance occurs in 18% of isolates, precluding empiric use. 3
• Moxifloxacin demonstrates 16.3% resistance rates among Prevotella species. 3

Metronidazole Considerations

• While metronidazole resistance remains rare (1.7% of isolates), emerging resistance necessitates periodic susceptibility monitoring. 3
• Metronidazole can be considered for empiric therapy but should be combined with susceptibility testing when feasible. 3

Ampicillin-Sulbactam

• Ampicillin-sulbactam shows intermediate resistance in 0.8% of isolates, with generally good activity, but the addition of a beta-lactamase inhibitor is essential given high ampicillin resistance. 3

Clinical Management Algorithm

Step 1: Assess Clinical Context

• If P. jejuni is isolated from jejunal biopsy in a patient with celiac disease: Focus on celiac disease management with strict gluten-free diet and dietitian consultation, as the organism likely represents altered microbiota rather than a primary pathogen. 4
• If P. jejuni is isolated from normally sterile sites (blood, abscess, deep tissue): Treat as a clinically significant infection requiring antimicrobial therapy. 1, 2

Step 2: Initiate Empiric Antimicrobial Therapy (for infections)

• Start piperacillin-tazobactam 3.375-4.5g IV every 6-8 hours, OR
• Cefoxitin 1-2g IV every 6-8 hours, OR
• Tigecycline 100mg IV loading dose, then 50mg IV every 12 hours. 3

Step 3: Obtain Antimicrobial Susceptibility Testing

• Request anaerobic culture with susceptibility testing using gradient test methodology or broth microdilution. 3
• Ensure testing includes ampicillin-sulbactam, piperacillin-tazobactam, cefoxitin, carbapenems, clindamycin, metronidazole, and fluoroquinolones. 3

Step 4: De-escalate Based on Susceptibility Results

• Narrow therapy to the most appropriate agent based on susceptibility patterns and clinical response. 3
• Consider transition to oral therapy when clinically appropriate, though oral options for anaerobes are limited. 3

Common Pitfalls to Avoid

• Do not assume P. jejuni isolated from intestinal biopsies in celiac disease patients requires antimicrobial treatment—focus on celiac disease management unless there is evidence of invasive infection. 1
• Do not use clindamycin, ampicillin, tetracycline, or fluoroquinolones empirically without documented susceptibility due to high resistance rates. 3
• Do not overlook the possibility of polymicrobial infection—Prevotella species often occur in mixed anaerobic infections requiring broader antimicrobial coverage. 3, 2
• Do not delay source control measures (drainage of abscesses, debridement of necrotic tissue) when P. jejuni is isolated from purulent collections. 2

Special Considerations for Celiac Disease Context

• When P. jejuni is isolated from jejunal biopsies in celiac disease patients, ensure proper celiac disease diagnosis with tissue transglutaminase IgA (tTG-IgA) and total IgA levels. 4, 5, 6
• Confirm celiac disease with duodenal biopsy showing villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes (≥25 per 100 enterocytes). 4
• Initiate strict gluten-free diet immediately after celiac disease confirmation and refer to a dietitian experienced in managing celiac disease. 4
• Monitor celiac serology at 6 months, 12 months, and annually thereafter to assess dietary adherence and mucosal healing. 4, 6