Nosocomial pneumonia is a significant health care issue, with an estimated 300,000 cases annually in the US and a crude mortality rate as high as 70%. The direct costs associated with nosocomial pneumonia have been calculated at over 2 billion dollars a year in the US.

The most common pathogens responsible for nosocomial pneumonia include Pseudomonas aeruginosa, Staphylococcus aureus, which is often methicillin-resistant, Enterobacter spp. and Acinetobacter spp. If the infection occurs within four days of hospitalization it is more likely to be caused by methicillin-susceptible Staphylococcus aureus (MSSA), Haemophilus influenzae, Escherichia coli, Proteus spp. or Streptococcus pneumoniae. If the infection develops after five days in hospital then it is more likely to be caused by methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa or Acinetobacter spp. Therefore the time of onset can be useful in determining the initial empiric therapy.

Initiation of appropriate empiric therapy is very important in optimizing outcome of nosocomial pneumonia. Research has shown that inadequate empiric therapy is given to 25-50% of patients and is associated with a mortality rate 2 to 3 times higher than that for patients given correct therapy, as well as a longer stay in ICU and hospital, increased use of mechanical ventilation and increased rate of organ system failure.

In order to treat nosocomial pneumonia effectively antimicrobial therapy needs to be initiated quickly, and combination therapy used where necessary. Fluoroquinolones are useful in this setting as they have a wide spectrum of activity, excellent bioavailability, a long half-life and penetrate into both the intracellular compartment as well as epithelial lining fluid.

No single antimicrobial can effectively treat all pathogens responsible for nosocomial pneumonia with pseudomonal resistance rates of 20% to ceftazidime and imipenem, 14% to piperacillin-tazobactam and 35% to ciprofloxacin. Therefore, appropriate therapy of Pseudomonas aeruginosa includes combination therapy with two antibiotics such as a fluoroquinolone plus β-lactam.

Efficacy of combination therapy is illustrated by results from an in vitro pharmacodynamic model demonstrating that when levofloxacin or imipenem were used alone there was significant overgrowth of resistant subpopulations, but when used in combination there was rapid eradication of all clinical isolates with no emergence of resistance.

High-dose therapy with levofloxacin has also been investigated in nosocomial pneumonia. The 750 mg dose has been advocated because this achieves higher AUC/ MIC ratios, a potentially useful feature in managing difficult-to-treat infections, with better penetration into various tissues, rapid eradication and prevention of resistance.

A 750 mg dose of levofloxacin was compared with 500 mg dose and ciprofloxacin 500 mg in healthy volunteers. The 750 mg dose achieved more than double the concentration in epithelial lining fluid and plasma compared to the other schedules.

Levofloxacin 750 mg was also associated with plasma AUC to MIC ratios of 108, a significant increase from 55 associated with 500 mg levofloxacin. These results have led to levofloxacin being approved for the treatment of nosocomial pneumonia due to MSSA, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, Pseudomonas aeruginosa (recommended with an anti-pseudomonal β-lactam).

A clinical trial in nosocomial pneumonia comparing levofloxacin 750 mg once daily IV switching to oral levofloxacin or imipenem cilastatin 500 mg or 1 g every 6-8 hours switching to 750 mg twice daily oral ciprofloxacin has been reported. Clinical success was approximately 60% for both arms, and the microbiological eradication was similar for both groups although more Pseudomonas aeruginosa was eradicated with high-dose levofloxacin than with imipenem.

Overall the clinical success rate for mechanically ventilated nosocomial pneumonia was equivalent between high-dose levofloxacin and imipenem. Analysis of the patient subgroup with bacteremia demonstrated no difference in outcome between levofloxacin and imipenem. There was no difference in adverse events between the levofloxacin and comparator arms.

Nosocomial pneumonia is a leading cause of death due to infection and is associated with increased morbidity, mortality and cost. The most frequent infecting pathogens include Gram-negative bacteria, especially Pseudomonas aeruginosa as well as Gram positives particularly MRSA. High-dose levofloxacin is as effective as imipenem cilastatin in the treatment of nosocomial pneumonia, is well tolerated and associated with reduced duration of intravenous therapy.