Dr Chu Thi Hanh
Head of Respiratory Department
Tam Anh General Hospital
According to the Survey of Antibiotic Resistance (SOAR) – an ongoing surveillance study of key respiratory pathogens – susceptibility to macrolides in South Korea was relatively low at 20% and ranged from 50% to 60% in Thailand, India and Singapore.1 The Asian Network for Surveillance of Resistant Pathogens (ANSORP) has also reported a high prevalence of macrolide resistance in Streptococcus pneumoniae isolates.2 Levofloxacin is a well established treatment option for lower respiratory tract infections (LRTI) – particularly since it is active against some macrolide-resistant respiratory pathogens.3
Dr Chu Thi Hanh – Head of Respiratory Department at Tam Anh General Hospital – provides an update on the treatment strategy for community acquired pneumonia (CAP) in Vietnam and shares her clinical experience with levofloxacin in the treatment of LRTI.
Q1. What are the current guidelines for the treatment of CAP in Vietnam? Have local efforts to improve antibiotic prescribing changed these guidelines in any way?
In Vietnam, we have guidelines for the diagnosis and treatment of adult CAP from the Ministry of Health of Vietnam 2020. These guidelines are similar to the guidelines of the American Thoracic Society (ATS) and Infectious Diseases Society (IDS) of America 2019. We have introduced our guidelines in scientific conferences, seminars by the Vietnam Respiratory Society and Ha Noi Respiratory Society, and during teaching of postgraduate doctors. Since these guidelines are approved by the Ministry of Health, they drive the diagnostic and treatment procedure in all hospitals and clinics in Vietnam. However, specific antimicrobial choice for specific indications is based on local resistance patterns. Unfortunately, in many areas in Vietnam, there is a lack of data on antibiotic resistance patterns. In addition, many people buy antibiotics without a prescription; the three most commonly sold antibiotics are amoxicillin, cephalexin and azithromycin. This poses a challenge for us when choosing antibiotics for these patients who self-prescribe and may have developed resistance. Hopefully, stricter management of antibiotic use will improve this problem.
Q2. What treatment is usually given for LRTI before hospital admission? What is the treatment strategy commonly used when patients are hospitalised for CAP?
The common LRTI conditions include acute bronchitis, pneumonia, exacerbations of obstructive pulmonary disease (COPD), exacerbations of bronchiectasis, and lung abscess. Antibiotic treatment should be considered in patients with LRTI with suspected or definite pneumonia and selected exacerbations of COPD or bronchiectasis. The choice of antibiotic depends on the specific status of the patient. For example, to treat an outpatient with pneumonia, we usually use monotherapy with a beta-lactam with or without beta-lactamase, or azithromycin or clarithromycin for young healthy patients. For patients with comorbidities such as chronic cardiovascular disease, lung, liver or renal disease, or diabetes mellitus, we may choose beta-lactam with/without beta-lactamase and a macrolide, or we use monotherapy with a respiratory fluoroquinolone like levofloxacin or moxifloxacin. In addition, symptoms such as symptomatic acute cough should be treated.
Similarly, in the inpatient setting, antibiotic treatment for CAP depends on the condition and history of the patient. In inpatient adults with non-severe CAP without risk factors for methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa, we choose a combination of beta-lactam with/without beta-lactamase and a macrolide, doxycycline or respiratory fluoroquinolone. In patients with severe CAP without risk factors for MRSA or P. aeruginosa, we often choose a third generation cephalosporine or carbapenem plus a respiratory fluoroquinolone or aminoglycoside. If the patient has risk factors for P. aeruginosa, we use beta-lactam/beta-lactamase or ceftazidime, cefepime or carbapenem plus a fluoroquinolone (levofloxacin). We will add vancomycin or linezolid for patients with risk factors for MRSA.
Q3. Is levofloxacin (as monotherapy or combination therapy) typically used after treatment failure with macrolides in CAP?
The guidelines from the IDSA/ATS as well as the new guidelines form the European Society of Clinical Microbiology and Infectious Diseases/European Respiratory Society (ECMID/ERS) recommend initial empirical therapy with a respiratory fluoroquinolone (e.g., levofloxacin, moxifloxacin) as monotherapy for non-severe CAP patients and in combination with a beta-lactam for severe CAP patients. In our clinical practice, we also often add a respiratory fluoroquinolone or an aminoglycoside in combination with a beta-lactam if the patient does not improve after treatment with macrolides. In fact, I prefer quinolones over macrolides because of the high rate of macrolide resistance in pneumococci.
Q4. What is your treatment experience with levofloxacin for CAP? Please provide common indications for conventional dose and high-dose levofloxacin in Vietnam and response rates in terms of efficacy and safety.
We usually use respiratory fluoroquinolones including levofloxacin for CAP inpatients especially after treatment failure with macrolides. These antibiotics are also used as first-line treatment in patients with comorbidities, severe airway obstruction or recurrent exacerbations of COPD or bronchiectasis. We have found that levofloxacin is active against most of the respiratory pathogens and has a good clinical success rate. A high dose (750 mg) of once-daily levofloxacin is approved for use in the US in the treatment of CAP. The IDSA/ATS guidelines for the diagnosis and treatment of adults with CAP also recommend using levofloxacin 750 mg daily. The high-dose, short-course levofloxacin regimen maximises its concentration-dependent bactericidal activity and may reduce the potential for resistance to emerge. In Vietnam, we usually use intravenous levofloxacin with a 750 mg daily dose for patients who are hospitalised for CAP. But in outpatients with CAP, we often choose oral levofloxacin 500 mg daily because we have only levofloxacin 500-mg tablets. But if levofloxacin 750 mg tablets are available, I prefer to use this dose because it is more effective and there are no additional side effects especially in patients who have comorbidities. Of course, if the patient’s renal function is declined, the dose needs to be changed. Some side effects that I have seen are allergic reactions, seizures, mood or behavioural changes, headache, sweating, trouble sleeping; but they are not very serious.
Q5. What is your experience with prescribing high-dose, short course levofloxacin for CAP patients with comorbidities and non-severe CAP? What are your considerations when prescribing this regimen?
As I said above, 750 mg of once-daily levofloxacin is one of the common choices for non-severe CAP patients with comorbidities and I often use it in a 5- to 7-day course. In these patients, I usually use levofloxacin in combination with a beta-lactam. In my experience, this high dose of levofloxacin is more efficient than a conventional dose. Some patients may have side effects when using this drug but they are often not serious. Before prescribing, I always ask patients about their medication history especially in terms of antibiotics use and allergies, as well as evaluate serum transaminase level and renal function. If the renal function is abnormal, we may have to decrease the dose. Patients should take levofloxacin at least two hours before or after antacids or preparations containing iron or zinc if they are on those medicines. Some patients may have inflammation of blood vessels when using intravenous levofloxacin so I usually ask the nurses to use a slow flow rate. In my opinion, levofloxacin is a valuable antimicrobial agent that has activity against a wide range of respiratory bacterial pathogens; however, its use should be considered carefully so that the potential for resistance selection can be minimised and its usefulness maximised in severe infections. Sometimes, we also have to be cautious when we suspect TB; we have to do a TB test before we use it.