Lower Respiratory Tract Infection (Pneumonia) - Chapter 4

18 July, 2023

So, I have talked about fluoroquinolone in CAP in many guidelines – the ATS guideline, IDSA guideline, and also our Thai guideline. In any setting of CAP – both OPD and hospitalized/ICU – you will see, we give any drug: beta-lactam plus advanced macrolide or fluoroquinolone; and even in some settings, we can give just monotherapy with fluoroquinolone. This will mean less fluoroquinolone. The advantage of fluoroquinolone in pneumonia is, you see from many data from many countries, very low resistance with community-acquired pathogens for over 20 years. Fluoroquinolone will give coverage for all bacteria, including Streptococcus pneumoniae – DRSP, Haemophilus influenzae, Klebsiella, and even Pseudomonas aeruginosa. In some settings, fluoroquinolone causes good killing as well. And secondly, this is also very, very important: the coverage of atypical pathogens, such as Legionella pneumophila, Chlamydia pneumoniae, and Mycoplasma. That is, in some settings, in some areas of Thailand, and in many countries, we do see increasing Legionella, Mycoplasma, and Chlamydia – more than 30%. So, fluoroquinolone has the advantage of coverage of both typical and atypical pathogens. And thirdly, the overall bioavailability. Fluoroquinolone has good PK/PD, as I am going to show you later on. Oral bioavailability is as good as parenteral, and also oral bioavailability has good tissue concentration. And fourthly, the convenience of monotherapy, particularly in the hospital setting – we just give parenteral treatment as only one drug, a one-time treatment. So that is really convenient and also cost saving. And also, with good PK/PD, we can switch from parenteral to oral treatment and switch the patient or discharge the patient to the outpatient setting soon. And lastly, the adverse effect of fluoroquinolone monotherapy is less than combination or better than ­beta-lactam plus advanced macrolide.

So, for fluoroquinolone, we call it the tissue-directed antibiotic because fluoroquinolone has good penetration to all tissues in the body. You can see here, the plasma level of levofloxacin 500 mg, levofloxacin 750 mg, or even ciprofloxacin. You can see epithelial lining fluid (ELF) is higher than plasma. That is why we call it a tissue-directed antibiotic. In some settings, it was twice in the plasma, and even in the alveolar space, it was even higher. This is why when giving fluoroquinolone in pneumonia treatment, the patient will respond faster than when given the beta-lactam antibiotic because the bacteria is now in the alveolar space. That’s why we give the higher concentration in the alveolar space.

In the beginning, we used fluoroquinolone at not that high a dose, but as time goes by, we increase the dose of fluoroquinolone, including levofloxacin. You see from the study, we compare 750 mg and 500 mg of levofloxacin.

All over, H. influenzae, H. parainfluenzae, Strep pneumoniae, Chlamydia, Legionella, and Mycoplasma are seen, and you see all severity, PSI class III, and PSI class IV. For levofloxacin high dose 750 mg for only 5 days versus 500 mg for 10 days, no inferiority was seen. So, it is better to give 750 mg for only 5 days.

And what about the clinical response of a higher dose of 750 mg for 5 days? You see the fever response both from patient reports and by medical personnel measuring the body temperature. You see that 750 mg fever response is faster than 500 mg. So, from this data, we should give 750 mg and not for a long duration.

Medical resource utilization of levofloxacin versus the standard regimen of ceftriaxone plus advanced macrolide azithromycin: In Thailand, the beta-lactam that we use for CAP is ceftriaxone over amoxicillin-clavulanate. Because with ceftriaxone, we can use one saline. So, in many studies, we compared levofloxacin with ceftriaxone plus azithromycin. Look at the length of stay and length of intravenous administration. Levofloxacin is much better than ceftriaxone plus azithromycin in both length of stay and length of intravenous parenteral injection. So, this is the advantage of giving levofloxacin in community-acquired pneumonia.