From the Guidelines
Gram-negative pneumonia should be treated with an antipseudomonal beta-lactam (such as piperacillin-tazobactam 4.5g every 6 hours, cefepime 2g every 8 hours, or meropenem 1g every 8 hours) plus an aminoglycoside or fluoroquinolone for 7-14 days, as recommended by the most recent guidelines 1.
Key Considerations
- The choice of empiric antibiotic therapy depends on the risk of mortality and the likelihood of multidrug-resistant (MDR) pathogens 1.
- For patients at low risk of mortality and without risk factors for MDR pathogens, monotherapy with a narrow-spectrum agent such as ertapenem, ceftriaxone, or levofloxacin may be sufficient 1.
- However, for patients at high risk of mortality or with risk factors for MDR pathogens, combination therapy with an antipseudomonal beta-lactam and an aminoglycoside or fluoroquinolone is recommended 1.
- The use of combination therapy may reduce mortality and improve outcomes in patients with severe infections, particularly those caused by MDR Gram-negative bacteria 1.
Antibiotic Options
- Antipseudomonal beta-lactams: piperacillin-tazobactam, cefepime, meropenem, imipenem 1.
- Aminoglycosides: gentamicin, tobramycin, amikacin 1.
- Fluoroquinolones: levofloxacin, ciprofloxacin 1.
Supportive Care
- Oxygen therapy, hydration, and respiratory support are essential alongside antibiotic treatment 1.
- De-escalation of antibiotics based on culture results is important to prevent resistance development 1.
From the FDA Drug Label
1.1 Nosocomial Pneumonia
Levofloxacin tablets are indicated for the treatment of nosocomial pneumonia due to methicillin-susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, or Streptococcus pneumoniae.
Gram-negative pneumonia can be caused by several bacteria, including:
- Pseudomonas aeruginosa
- Serratia marcescens
- Escherichia coli
- Klebsiella pneumoniae
- Haemophilus influenzae
Levofloxacin is indicated for the treatment of nosocomial pneumonia due to these gram-negative bacteria. 2
From the Research
Gram-Negative Pneumonia Treatment
- The combination of levofloxacin and ceftazidime has been shown to be effective in treating Gram-negative hospital-acquired pneumonia (HAP) in the intensive care unit (ICU) 3.
- New antibiotics such as ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam have potent activity against carbapenem-resistant Enterobacterales, including Klebsiella pneumoniae carbapenemase producers 4.
- Cefiderocol may also play an important role in the management of pneumonia caused by Acinetobacter baumannii, along with plazomicin and eravacycline 4.
Epidemiology and Diagnosis
- Gram-negative pulmonary infections are increasing worldwide, and traditional assumptions that these are limited to hospital and ventilator-acquired pneumonia are rapidly falling away 5.
- Rapid, multiplex PCR-based detection of a wide variety of potential pathogens offers the opportunity to replace empiric antibiotic choices with targeted, evidence-based therapy in clinically actionable timeframes 5.
Comparative Studies
- A comparative study of cefepime and ceftazidime in the treatment of community-acquired lower respiratory tract infections found that both drugs were well tolerated and had similar clinical cure rates and pathogen eradication rates 6.
- Meropenem has been shown to have a broad spectrum of in vitro activity against Gram-positive and Gram-negative pathogens, including extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae, and has similar efficacy to comparator antibacterial agents in various infections 7.