What is the next step in treating pneumonia that is unresponsive to levofloxacin (fluoroquinolone)?

Treatment of Pneumonia Unresponsive to Levofloxacin

For pneumonia that is unresponsive to levofloxacin, the recommended next step is to switch to a combination therapy of a beta-lactam (such as cefotaxime, ceftriaxone, or co-amoxiclav) plus a macrolide (such as clarithromycin or erythromycin). 1, 2

Assessment of Treatment Failure

• When a patient fails to respond to initial levofloxacin therapy, conduct a thorough review by an experienced clinician of the clinical history, examination, prescription chart, and results of all available investigations 1, 3
• Consider additional investigations including repeat chest radiograph, CRP and white cell count, and further specimens for microbiological testing 1, 2
• Review microbiological data to exclude Staphylococcus aureus and Gram-negative bacillary infection 1
• Verify compliance with and adequate absorption of the oral regimen if applicable 1

Alternative Antibiotic Options

For Non-Severe Pneumonia:

• Change to a combination of a beta-lactam (co-amoxiclav, cefuroxime, cefotaxime, or ceftriaxone) plus a macrolide (clarithromycin or erythromycin) 1, 4
• If the patient has a beta-lactam allergy, consider clindamycin as an alternative 1

For Severe Pneumonia:

• For patients already on combination therapy, add coverage for MRSA if suspected 1, 2
• Consider an antipseudomonal agent (piperacillin-tazobactam, cefepime, meropenem) if Pseudomonas aeruginosa is a concern, particularly in patients with risk factors 1, 2
• The addition of rifampicin may be considered for those with severe pneumonia not responding to combination antibiotic treatment 1

Considerations for Specific Pathogens

• If DRSP (drug-resistant Streptococcus pneumoniae) is suspected, consider using a newer fluoroquinolone with better pneumococcal coverage (moxifloxacin, gatifloxacin) or vancomycin 1
• For pneumococcal MIC values to penicillin at 4 mg/L or greater, therapy should be with a newer antipneumococcal fluoroquinolone, vancomycin, or clindamycin 1
• If staphylococcal pneumonia is suspected, add flucloxacillin (for MSSA) or vancomycin (for MRSA) 1, 3

Route of Administration and Duration

• For patients requiring hospitalization, use parenteral antibiotics initially 1, 2
• Transfer to oral therapy when clinical improvement occurs and temperature has been normal for 24 hours, providing there is no contraindication to the oral route 1
• For severe, microbiologically undefined pneumonia, 10 days of treatment is recommended 1, 4
• Extended treatment (14-21 days) is recommended when legionella, staphylococcal, or Gram-negative enteric bacilli pneumonia are suspected or confirmed 1, 2

Common Pitfalls and Caveats

• Fluoroquinolone resistance in pneumococci, while still relatively uncommon (< 2% in the US), is increasing and can develop during therapy 1, 5
• Levofloxacin failures have been reported in cases of pneumococcal pneumonia, even with penicillin-sensitive strains 5
• Delaying appropriate antibiotic therapy can increase mortality, so prompt reassessment and change of antibiotics is essential when treatment failure is suspected 1, 3
• Vancomycin should have a limited role and be reserved for patients with high-level resistance who are failing other therapies 1

Monitoring Response to New Treatment

• Monitor clinical response daily, including temperature, respiratory and hemodynamic parameters 3
• Consider measuring C-reactive protein on days one and three/four, especially in patients with unfavorable clinical parameters 2
• Arrange clinical review for all patients at around 6 weeks, with a chest radiograph for those with persistent symptoms or physical signs 4