For the practical treatment, we start empiric antibiotics based on number one: (1) severity of pneumonia: if the patient is not severe by the score (we have many scores: CURB-65 and PSI), if the patient does not look sick, and if the patient is able to tolerate some activity, we called it walking pneumonia in the old days and we classify it as outpatient pneumonia. And without comorbidities, no diabetes, no other comorbidities, and no previous colonization of Pseudomonas aeruginosa, the guidelines of the American Thoracic Society (ATS) – and Infectious Diseases Society of America, recommend to use amoxicillin or doxycycline. Amoxicillin may be okay. But regarding doxycycline in Thailand, we don’t recommend doxycycline to treat CAP at all because our Strep pneumoniae are highly resistant to doxycycline. Anyway, even for outpatient CAP or walking CAP, in Thailand, we do not recommend giving amoxicillin. We prefer amoxicillin-clavulanate or cephalosporin plus advanced macrolide and no doxycycline in Thailand. Most ID doctors or even chest doctors do not recommend doxycycline. And also, with these, sometimes we recommend instead of giving a combination of amoxicillin-clavulanate or cephalosporin plus advanced macrolide, we prefer monotherapy with respiratory fluoroquinolone.
For patients who need hospitalization, so-called hospitalized pneumonia, we prefer (I think not just us, ATS and IDSA these days also recommend) starting with parenteral beta-lactam plus macrolide. In this recommendation, we mean advanced macrolide, for example, amoxicillin-clavulanate or third-generation cephalosporin plus azithromycin or monotherapy with respiratory fluoroquinolone.
And with the risk of MRSA, as I mentioned earlier, in Thailand, we don’t see MRSA. In both community-acquired and hospital-acquired pneumonia, we don’t see MRSA. But we have started to see Pseudomonas aeruginosa pneumonia. If we suspect Pseudomonas aeruginosa pneumonia, as I mentioned earlier, with the risk factors, we start with piperacillin/tazobactam or ceftazidime, minus/plus aminoglycoside amikacin, depending on the severity of the patient by using the PSI score or CURB-65 score.
So, this concept – hit hard and hit fast, we have heard this for many, many years, as Paul Ehrlich stated more than 10 or 100 years ago. But we started to use this over 15 years ago; Thomas has mentioned that for pneumonia, in the beginning, if we give the appropriate treatment, the patient can survive, the mortality rate will be low, and no morbidity will be there at all. So, this is the concept of treatment of CAP and hospital-acquired pneumonia by using the strategy of hit hard and hit fast. Hit hard means you start with the appropriate or higher dose. Particularly, if we use the beta-lactam antibiotic, we might have to give the loading dose. Or if we give fluoroquinolone, we have to give a higher dose as PK/PD. And hit fast means to give an empiric treatment. So, the patient will respond quite fast, and also, this will reduce the morbidity and reduce other complications. Advantage of hit hard is that you give a high average steady state within 48 hours; particularly the concentration of antimicrobial drugs will cover the MIC90 and prevent resistant strains. So, in some groups of antibiotics, we give the loading dose. Particularly for beta-lactam like cephalosporin or amoxicillin-clavulanate, we give the loading dose, but for fluoroquinolone, we give the appropriate dose since the beginning.
So, to start the empiric antibiotic, we give a higher dose, an appropriate dose. Now, coming to the duration, how long to give the antibiotic in the treatment of CAP? As I mentioned earlier, if we start with an appropriate drug and an appropriate dose, the duration should not be long. So, we follow by resolution of vital signs, for example, fever, heart rate, respiratory rate and blood pressure (when all clinical signs are close or back to normal). Usually, we will continue the antibiotic for a few days after normalization of those clinical signs. Anyway, the total antibiotic duration should not be less than 5 days. But many studies have shown that if we start with an appropriate drug and an appropriate dose, the duration should be around 5 to 10 days. Anyway, still in some settings, a longer course of antibiotic therapy will be recommended for: number one, pneumonia complicated by extrapulmonary complications, such as meningitis, endocarditis, or other deep-seated infections that we rarely see. Particularly if we give the appropriate antibiotic at the beginning, we will not see extrapulmonary complications. Secondly, pneumonia with less common pathogens, particularly those in the southeast part of Thailand, we do see a lot of Burkholderia pseudomallei, so-called melioidosis. So, our Thai guideline for community-acquired pneumonia in the northeastern part of Thailand, the core antibiotic will be ceftazidime minus/plus fluoroquinolones or minus/plus cotrimoxazole for Burkholderia pseudomallei, until we have the culture back.
As I mentioned, we give an appropriate drug and an appropriate dose. So, we don’t have to give a longer duration. What is the impact of shortening the duration? The advantage of shortening the duration: number one, you will prevent or delay the development of multi-resistant strain, so-called no emergent resistant, during treatment; we will not see it. If we give for too long a duration, we allow the bacteria to mutate, to produce some substance, and to develop resistance. And also, for a short duration, the patient will be willing to take the medicine or will be willing to stay in the hospital for a short time with better compliance; also, this is cost-saving, and also, this reduces adverse effects.