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Management of community-acquired pneumonia CAP and AECB may pose challenges because of diagnostic difficulty in differentiating infections caused by typical and atypical microorganisms and rising rates of antimicrobial resistance. Beta-lactam antibiotics, macrolides, and fluoroquinolones are routinely prescribed medicines for the management of ALRTIs.

Macrolides are time-tested and effective agents for the treatment of LRTIs. According to the Global Burden of Disease study GBD , chronic obstructive pulmonary disease COPD and lower respiratory tract infections LRTIs represent the third and fourth most common causes of death, respectively, after ischemic heart disease and cerebrovascular disease.

Annual incidence of pneumonia, one of the most important LRTIs, is reported to be The rates differ based on the age, with higher incidence observed in patients between 65 and 79 years of age Children younger than 5 years are commonly affected, making it the highest contributor of death due to LRTIs in them.

The annual incidence of CAP is about 5—11 per 1, population with higher rates reported in the elderly population. In this article, the published literature on LRTIs and its management is reviewed with special focus on clarithromycin.

Review articles, clinical trials, clinical practice guidelines, and experimental studies published from onward were considered for writing the review. Table 1 provides criteria for different types of LRTIs. In routine clinical practice, it is difficult to differentiate between different diseases without diagnostic tests because of the considerable overlap in clinical presentation.

Considering difficulties in performing full diagnostic workup in every patient, empirical and practical approach is necessary. Patients with atypical pneumonia have slightly different course than typical pneumococcal pneumonia.

Otherwise, many clinical features of typical and atypical pneumonia are similar. It is important to differentiate infection from that of noninfectious disorders such as asthma, COPD, heart failure, or lung infarction.

Due to their nature and ongoing treatment, these chronic noninfectious disorders can be identified based on clinical and medication history. It is also important to differentiate pneumonia from other respiratory infections.

Common bacterial pathogens responsible for typical pneumonia include Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, and Haemophilus influenzae [ 12 ] whereas microorganisms causing atypical CAP include Legionella pneumophila, Mycoplasma pneumoniae, Chlamydophila pneumoniae , and Chlamydia psittaci. Gastrointestinal symptoms, headache, confusion, hemoptysis, dyspnea, and musculoskeletal complaints in the form of myalgia and arthralgia are possible symptoms in these patients.

Bullous myringitis, though not common, is a characteristic feature. Pharyngitis and crepitations may be observed on clinical examination. A weighted point system of syndromic diagnosis is useful for differentiating it from other pneumonia. Other organisms must also be considered in light of the patient's risk factors and severity of illness. Information on the etiology of CAP is required for treatment and preventive purposes.

Chest X-ray is the most common and useful investigation for the diagnosis of CAP. Posteroanterior PA and lateral view should be taken in adults suspected of pneumonia, whenever possible.

Usually, chest X-ray in typical bacterial CAP shows the presence of segmental or lobar consolidation. Typical pneumonia is often associated with elevations in total leukocyte count, erythrocyte sedimentation rate, and C-reactive protein CRP. In atypical pneumonia, these investigations may be normal or slightly increased.

Sputum stains and culture are relatively insensitive tests with limited specificity for the diagnosis of pneumococcal pneumonia. On the one hand, in many cases, sputum culture may be negative, whereas on the other hand, there are chances of false-positive report because of the nasopharyngeal carriage.

Clinical utility of blood and pleural culture in routine clinical practice is limited because of low yield of positive rates of S. Additional investigations such as serological test, enzyme immunoassays, complement fixation method, polymerase chain reaction PCR , and antigen detection may be required in some patients, especially if they do not respond to antibiotic therapy. A study from Sri Lanka showed less reliability of cold agglutinin detection as compared to specific antibody detection by isotype ELISA for diagnosis of M.

Short time for sample processing and ability to detect as many as Early identification of high-risk patients is important for the prevention of complications.

The CURB scoring system has been validated in a hospital-based prospective study in Indian patients. However, robust data comparing benefits of one over the other are limited. The main goals of treatment of CAP are to eradicate the causative microorganisms, provide relief to the patient, and reduce the risk of hospitalization and reinfection. Despite extensive investigations, in many patients, the etiology of CAP remains undetected.

The bacteria causing typical pneumonias usually respond to beta-lactam antibiotics. However, the atypical pathogens, being intracellular organisms, do not respond to beta-lactam antibiotics.

The NICE guidelines[ 22 ] recommend considering a point-of-care CRP test in patients with symptoms of LRTI; in case, diagnosis is not made after clinical assessment or there is confusion regarding initiating antibiotic therapy.

Decision to start antibiotic therapy can be made based on the level of CRP [ Table 2 ]. Considering these challenges, empiric, broad-spectrum antibacterial therapy, providing coverage against common bacteria responsible for CAP as well as atypical microorganisms is often selected.

Drug-related factors including pharmacological profile, safety profile, risk of drug interactions, and cost and patient-related factors such as severity of disease, comorbidities, clinical presentation, and local resistance pattern[ 31 ] are important while selecting an empirical therapy. In this regard, macrolides represent useful agents for the treatment of CAP caused by typical as well as atypical bacteria.

Macrolides offer several benefits in the management of respiratory infections because of their complementary action along with primary antimicrobial activity. Due to high tissue penetration, anti-inflammatory properties, and action on immune system, macrolides can reduce inflammatory responses.

Clarithromycin has a broad spectrum of antibacterial activity, improved pharmacokinetic and pharmacodynamic properties, and better tolerability compared to erythromycin.

Tissue concentration and concentration in the alveolar macrophages are about 2—20 times and times higher than serum levels, respectively. Efficacy and safety of clarithromycin has been demonstrated in several clinical trials in patients with respiratory diseases.

However, head-to-head comparative trials between clarithromycin and azithromycin are limited. Bonvehi et al. Some patients especially those hospitalized because of CAP need treatment with combination of antimicrobials, often used as empirical treatment. A study compared the combination of beta-lactam antimicrobial with macrolide therapy versus fluoroquinolone monotherapy in patients with severe CAP. The results of this study showed better outcomes with combination therapy for severe cases.

For class V pneumonia, severity index day and day mortality rate with combination therapy was 8. The corresponding rates with fluoroquinolone monotherapy were There was no difference in mortality rates between two arms for less severe disease. However, a retrospective study design was the limitation of this study. Larger randomized clinical trials are required to provide exact place of combination therapy in the treatment of CAP.

Amoxicillin is a preferred antimicrobial agent for initial empiric therapy in outpatients. Macrolides clarithromycin and azithromycin are recommended for patients with hypersensitivity to penicillins.

In India, consequent to the high prevalence, possibility of concomitant tuberculosis should be kept in mind while selecting pharmacological therapy for the management of respiratory infections. Inappropriate use of antimicrobials such as fluoroquinolones can increase the risk of fluoroquinolone-resistant M.

In addition, there could be a chance of masking active tuberculosis. COPD is an inflammatory condition. Moreover, infections can further increase the inflammatory response in acute exacerbations.

Clarithromycin is considered as one of the standard therapies for the treatment of AECB. The other agents used are amoxicillin mg tid and cefuroxime axetil mg bid for 7 days. The respiratory fluoroquinolones such as gatifloxacin and gemifloxacin have been compared with these standard therapies in clinical trials.

Clarithromycin is shown to be effective and well tolerated in the treatment of adults with AECB. In the GLOBE trial, clinical success rate and bacteriological success rate with clarithromycin were Clarithromycin was one of the antimicrobials among standard therapies.

In the presence of comorbidities or other risk factors for DRSP infection, either a respiratory fluoroquinolone moxifloxacin, gemifloxacin, or levofloxacin or combination of beta-lactam plus a macrolide or amoxicillin-clavulanate is preferred.

In patients with comorbidities or use of antimicrobials for the past 3 months or other risk factors for DRSP infection, combination of beta-lactam plus a macrolide is recommended strong recommendation; Level I evidence. The guideline suggests macrolide or tetracycline in case of allergy to penicillin.

In patients with moderate-to-severe CAP, dual therapy with amoxicillin and macrolide is suggested. Similarly, in highly severe CAP, dual therapy with a beta-lactamases-table beta-lactam and macrolide is suggested. According to the European Respiratory Society—The European Society for Clinical Microbiology and Infectious Diseases guideline, amoxicillin or tetracycline is recommended as the choice of antibiotic.

Macrolide is recommended as an alternative in case of hypersensitivity to first-line agent. Indian guidelines also recommend the use of macrolide in the treatment of CAP. In outpatients with comorbidities, oral combination of beta-lactams plus macrolide is recommended. For hospitalized patients in non-ICU and ICU setting, without risk factor for Pseudomonas aeruginosa , combination of beta-lactam plus macrolide is recommended.

Unlike other agents such as beta-lactams and fluoroquinolones, macrolides prevent the release of pro-inflammatory protein toxins and production of bacterial adhesins and biofilm, i. Mucus production is suppressed due to inhibition of muc5ac gene expression. Protection of ciliated respiratory epithelium and downregulation of the pro-inflammatory activities of epithelial cells are the other benefits of clarithromycin. In patients with chronic respiratory illness, clarithromycin can induce apoptosis in lymphocytes in the lungs.

LRTIs are common problems in day-to-day clinical practice. Antimicrobial therapy is a principal management component for these diseases. It is often difficult to diagnose and differentiate atypical infections from that of typical infections.

Clinical findings and radiological imaging may help to suspect atypical infections. In country like India, it is often difficult to confirm the atypical infection even in the laboratories because of the inherent properties of atypical bacteria, limited access to the sophisticated laboratory methods, and cost. In such a scenario, physician often resorts to empirical therapy with antimicrobial agents.

With growing evidence of antimicrobial resistance, empirical treatment is becoming more difficult. The antimicrobial agent is often selected based on the patient profile, local resistance pattern, availability of the medicine, and cost. Macrolide is an effective therapy for patients with LRTIs, i.


Management of lower respiratory tract infection in outpatient settings: Focus on clarithromycin

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