The most notable findings of our study are the following: 1. MDR pathogens are frequently (20.1%) isolated in BE exacerbations, with a higher proportion among hospitalized patients (24.5%); 2. The principal MDR microorganisms were Pseudomonas (46%), MRSA and ESBL+ Enterobacteriaceae; 3. Independent MDR risk factors were prior MDR isolation, hospitalization in the previous year and chronic renal disease.
Due to the structural changes in permanently dilated airways, bronchiectasis courses with recurrent infections and exacerbations. Pathogens involved depend on several aspects: lung function, advanced phase of the disease and patient comorbidities. [1, 2, 12] However, little is known regarding frequency and factors associated with isolation MDR at exacerbations [13].
We found that in 20% of exacerbations MDR pathogens were isolated and the most frequent were Pseudomonas, MRSA and ESBL+ Enterobacteriaceae. We evaluated resistance using conventional methods usually performed in daily routine and we don’t perform automated methods or clonal analysis of resistance. [14] The percentage and spectrum of MDR is more similar to nosocomial than to community-acquired infections, in line with the current approach to those problematic pathogens based on host characteristics and prior treatments, [3, 13, 14] and slightly higher than that reported by McDonnell et al. [15] In fact, MDR exacerbations occurred in elderly patients with a higher proportion of comorbid conditions, indicating associations with more debilitating diseases, requiring more contacts with health resources. Our results showed that the use of prior inhaled antibiotics and long-term oxygen therapy was greater in patients with MDR pathogens. Interestingly, no differences were found with regard to the use of bronchodilators or inhaled corticosteroids. Metersky et al. [16] have reported that, in health-care associated pneumonia, inhaled corticosteroids were associated with Pseudomonas etiology, although they found no association with resistance.
The spectrum of microorganisms identified, [17] whether treated as outpatients or in hospital, was similar except for the fact that MDR was barely encountered in outpatients. [18] The fact that MDR exacerbations were more frequently admitted is clinically relevant because exacerbations that require hospitalization have been reported to be associated with an increase in 1-year mortality. [19]
In our study, we found three independent MDR risk factors: renal disease, prior MDR isolation and hospitalization in the previous year. Chronic renal disease is a recognized MDR risk factor, as reported in pneumonia studies. [3] Shindo et al., [20] identified 6 independent MDR risk factors, regardless of whether the patient has health-care associated or community-acquired pneumonia, suggesting that risk factors relied more on host factors than on the setting of infection. Prior hospitalization is a fairly widely recognized independent MDR risk factor and specifically for MRSA, [21] and for Enterobacteriacea mainly related to exposure to III/IV generation of cephalosporins or broad-spectrum penicillins. [22]
Prior MDR isolation was independently associated with a higher risk of MDR exacerbation. In our cohort, approximately 50% of patients had chronic Pseudomonas infection, [23] reflecting the most severe patients seen in a specific BE clinic. Prior MDR colonization is a recognized risk factor for MRSA [24, 25] and for Pseudomonas [26] in COPD patients. We found that 40% of patients with MDR exacerbations had prior isolation with the same microorganism.
The proportion of MDR exacerbations was higher among those patients with higher FACED and BSI scores, as expected in more advanced BE disease, with more proportion of exacerbations and hospitalizations. Almost 80% of MDR exacerbations occurred in patients with higher punctuations in prognostic scales such as FACED or BSI whereas MDR in mild scales were lower 6.2% and 40.6% respectively. However, after entering in the model other independent factors, these scales are not remaining independently associated with multi-drug resistance.
With regard antimicrobial susceptibility, MDR exacerbations received less appropriate treatment than non-MDR, thus also requiring more changes in antibiotic regimens although without statistical differences. In fact, the choice of initial treatment was microbiological suitable in 75% of cases, probably because physicians took into consideration prior MDR colonization, [27] a policy that is supported by our findings. Currently, factors considered in the antibiotic selection include extent of the disease, severity, local resistance patterns, and prior culture results. [28] A practical conclusion is that extended-spectrum antibiotics against MDR could be withdrawn in patients with no risk factors and indicated if 2 or more risk factors are present. Where 1 risk factor is present, an extended-spectrum antibiotic may be indicated until MDR pathogens have been ruled out; a microbiological work-up should therefore be implemented. [29] Nevertheless, these recommendations need to be validated in different populations or BE subsets [30] and knowledge of local resistance rates and colonization rates should be considered. This policy may contribute to containing broad-spectrum coverage for MDR in unnecessary episodes and this strategy may contribute to curbing the future emergence of resistant microorganisms in this population.
Patients with MDR exacerbations required more hospitalizations and greater use of antibiotics although without longer hospital stay. In general, MDR infections have been associated with a higher number of days of hospitalization, [31] with higher antibiotic requirements, more hospitalization, [32] more use of health resources, with the attendant higher costs, and may eventually have a negative impact on prognosis. [33] Nevertheless, we consider that one-year follow-up could be insufficient for evaluating the potential clinical impact of MDR exacerbations and probably for that aim more subsequent exacerbations should be assessed.
Limitations
Pathogen identification relied mainly on conventional microbiological tests and invasive respiratory samples were only indicated if required by the attending physician; this is a real clinical scenario common in clinical hospital settings. No quantitative bacteriology measuring with colony counts was quantified in sputum. Due to the number of patients in the cohort, a secondary analysis to separate specific risk factors for each microorganism was not undertaken. Mild episodes of exacerbations treated in primary care and not evaluated in our specific clinics were not included.
Strengths
This is the first study aimed at identifying risk factors for MDR exacerbations with potential impact on clinical decisions for antibiotic choice. At present, BTS guidelines [28] suggest combination therapy rather than single-drug antibiotic therapy if a resistant strain of P aeruginosa is isolated. Our findings could be useful for avoiding unnecessary broad-spectrum antibiotics in patients without MDR risk factors.