Management of Persistent Enteric Fever Despite Meropenem Therapy
For enteric fever caused by Salmonella with persistent fever despite 2 weeks of meropenem therapy, switching to oral azithromycin is recommended as the most effective alternative treatment option. 1
Evaluation of Treatment Failure
When enteric fever persists despite appropriate antimicrobial therapy, consider the following:
- Evaluate for drug resistance patterns, as Salmonella strains may have developed resistance to multiple antibiotics including carbapenems 2
- Check for sequestered foci of infection (e.g., undrained abscesses) that may require drainage 3
- Consider malabsorption of oral antibiotics in previous treatment attempts 3
- Rule out other concurrent infections such as Clostridium difficile that may complicate the clinical picture 3
Treatment Protocol for Persistent Enteric Fever
First-line Alternative Therapy
Alternative Options if Azithromycin Cannot Be Used
- Combination therapy with meropenem plus azithromycin if severely ill 4
- Consider fluoroquinolones only if susceptibility is confirmed, as many Salmonella strains now show reduced susceptibility to ciprofloxacin 5
- Third-generation cephalosporins (ceftriaxone or cefixime) if susceptibility testing confirms effectiveness 5
Monitoring Response to Treatment
- Monitor fever pattern daily - expect defervescence within 5-8 days of starting effective therapy 4
- Repeat blood cultures if fever persists beyond 7 days on new antimicrobial regimen 3
- Evaluate for complications such as intestinal perforation or metastatic infections 3
Important Considerations
- Drug susceptibility testing is crucial for guiding therapy in persistent cases 3
- Patients with Salmonella bacteremia may remain febrile for 5-7 days despite effective therapy, requiring careful observation 3
- For recurrent Salmonella septicemia (especially in immunocompromised patients), consider 6 months or more of antibiotic treatment as secondary prophylaxis 3
- Imaging studies (ultrasonography, CT, or MRI) may be needed to detect complications such as aortitis, mycotic aneurysms, or extra-vascular foci of infection 3
Cautions and Pitfalls
- Reduced fluoroquinolone susceptibility is clinically significant and may lead to treatment failure despite laboratory reports indicating susceptibility 6
- Nalidixic acid resistance is a marker for potential fluoroquinolone treatment failure 6
- Household contacts should be evaluated for asymptomatic carriage to prevent recurrent transmission 3
- Avoid empiric switching of antibiotics without confirming susceptibility patterns 3
The evidence strongly supports that azithromycin is effective against extensively drug-resistant Salmonella strains and should be the preferred alternative when meropenem fails 1, 4.