Managing Mycobacterium avium Complex Lung Disease With a Little Help From My Friend.

Management of Mycobacterium avium complex (MAC) lung disease is complicated, frequently unsuccessful, and frustrating to patients and clinicians. The initial treatment effort may not be directed solely at MAC infection, rather it is often initiating airway clearance measures for bronchiectasis. The next important steps are deciding who to treat and when to initiate therapy. Definitive or unambiguous guidance for these decisions is often elusive. The evidence supporting the current macrolide-based regimen for treating MAC lung disease is compelling. This regimen has been recommended in consensus nontuberculous mycobacterial treatment guidelines from 1997, 2007, and 2020, although clinician compliance with these recommendations is inconsistent. Understanding the idiosyncrasies of MAC antibiotic resistance is crucial for optimal antibiotic management. As a corollary, the importance of avoiding development of macrolide resistance due to inadequate therapy cannot be overstated. An inhaled liposome amikacin preparation is now approved for treating refractory MAC lung disease and holds promise for an even broader role in MAC therapy. Surgery is also an important therapeutic adjunct for selected patients. Microbiologic recurrences due either to new infection or treatment relapse/failure are common and require the same level of rigorous assessment and clinical judgment for determining their significance as initial MAC isolates. In summary, treatment of patients with MAC lung disease is rarely straight forward and requires familiarity with multiple factors directly and indirectly related to MAC lung disease. The many nuances of MAC lung disease therapy defy simple treatment algorithms; however, with patience, attention to detail, and perseverance, the outcome for most patients is favorable.

Ternary nanoparticle complex of antibiotic, polyelectrolyte, and mucolytic enzyme as a potential antibiotic delivery system in bronchiectasis therapy.

Antibiotic-polyelectrolyte nanoparticle complex (or nanoplex in short) has been recently demonstrated as a superior antibiotic delivery system to the native antibiotic in bronchiectasis therapy owed to its ability to overcome the lung's mucus barrier and generate high localized antibiotic exposure in the infected sites. The present work aimed to further improve the mucus permeability, hence the antibacterial efficacy of the nanoplex, by incorporating mucolytic enzyme papain (PAP) at the nanoplex formation step to produce PAP-decorated antibiotic-polyelectrolyte nanoplex exhibiting built-in mucolytic capability. Ciprofloxacin (CIP) and dextran sulfate (DXT) were used as the models for antibiotics and polyelectrolyte, respectively. The results showed that the PAP inclusion had minimal effects on the physical characteristics, preparation efficiency, and dissolution of the CIP-DXT nanoplex. The optimal CIP-(DXT-PAP) nanoplex exhibited size and zeta potential of approximately 200 nm and -50 mV with CIP and PAP payloads of 60% and 32% (w/w), respectively. The nanoplex was prepared at high efficiency with larger than 80% CIP and PAP utilization rates. The CIP-(DXT-PAP) nanoplex exhibited tenfold improvement in the mucus permeability compared to its CIP-DXT nanoplex counterpart, resulting in the former's superior bactericidal activity against clinical Pseudomonas aeruginosa biofilm in the presence of mucus barrier. A trade-off, nevertheless, existed between antibacterial efficacy and cytotoxicity towards human lung epithelium cells upon the incorporation of PAP above a certain concentration threshold. Therefore, the optimal dosing of the CIP-(DXT-PAP) nanoplex must be carefully determined.

Clinical characteristics and outcomes of patients with Escherichia coli in airway samples.

PURPOSES: Escherichia coli is one of the most common pathogens in nosocomial and community-acquired infections, but is an uncommon respiratory pathogen. However, this pathogen may at times be seen in respiratory secretions. The study aims to determine the clinical and prognostic value of E. coli in respiratory secretions. METHODS: Cultures of respiratory secretions from hospitalized and outpatients between 2009 and 2016 were screened for isolation of E. coli. We defined three groups of patients: "Sensitive (S)"-growth of E. coli sensitive to all antimicrobials tested; Intermediate (I)-resistant to 1-2 antimicrobial classes; and "Resistant (R)"-resistant to at least three antibiotic classes. We compared factors associated with resistant strains and outcomes between the groups. RESULTS: Eighty patients with E. coli isolates from respiratory secretions were identified while screening 177 712 (4.5: 10 000 samples). Of the E. Coli-positive cultures, 11 were from ambulatory patients, 31 patients were hospitalized and 37 were hospitalized and intubated. Ten people had bronchiectasis and 29 had COPD. Patients with resistant E. coli had significantly more hospitalization days prior to positive culture (S = 1.2 ± 1.89 days, I = 1.23 ± 1.5 days and R = 3.7 ± 5.4 days, respectively; P = 0.002). Mortality was higher in patients with a resistant strain (R) versus (I) or (S) (76.7%, 31.8% and 26.7%, respectively; P < 0.0001) and remained significantly elevated after correction for prior hospital days. CONCLUSIONS: Pulmonary infection due to E. coli is uncommon. Isolation of resistant E. coli is associated with length of previous hospitalization, elevated mortality and may be viewed as a nosocomial pathogen.

Efficacy of inhaled ciprofloxacin agents for the treatment of bronchiectasis: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of inhaled ciprofloxacin agents in the treatment of patients with bronchiectasis is controversial. The objective of the study was to review systematically the efficacy of inhaled ciprofloxacin agents in patients with bronchiectasis. METHODS: We searched PubMed, EMBASE, and Cochrane Library databases for randomized controlled trials (RCTs) evaluating inhaled ciprofloxacin agents among patients with bronchiectasis. Data were pooled using a meta-analysis technique. RESULTS: Two phase II and four phase III RCTs were included with a total of 1685 patients. Treatment durations of phase III studies were 48 weeks, while those of phase II studies were shorter. Pooled analysis of overall studies exhibited a statistically significant benefit of inhaled ciprofloxacin agents in three exacerbation outcome measures, including time to first exacerbation (hazard ratio 0.74, 95% confidence interval [CI] 0.63-0.86, I2 23%), exacerbation frequency (risk ratio [RR] 0.73, 95% CI 0.61-0.86, I2 42%), and exacerbation proportion (RR 0.85, 95% CI 0.76-0.96, I2 25%) without significant heterogeneity. Outcomes evaluating pulmonary function, quality of life, and adverse events were not significantly different between the two groups. Although eradication of respiratory pathogens was more frequently observed, the emergence of ciprofloxacin resistance was also significantly higher in the ciprofloxacin group. CONCLUSIONS: A meta-analysis of RCTs of inhaled ciprofloxacin agents showed clinical benefit in terms of pulmonary exacerbations in patients with bronchiectasis. Since a significant increase of resistance was also noticed, clinical trials with a longer study period are required for a conclusive assessment. The reviews of this paper are available via the supplemental material section.

Antimicrobial susceptibility and impact of macrolide antibiotics on Moraxella catarrhalis in the upper and lower airways of children with chronic endobronchial suppuration.

INTRODUCTION: Moraxella catarrhalis is an important but insufficiently studied respiratory pathogen. AIM: To determine antibiotic susceptibility and impact of recent antibiotics on M. catarrhalis from children with chronic endobronchial suppuration. METHODOLOGY: We cultured nasopharyngeal (NP) swabs and bronchoalveolar lavage (BAL) fluids collected from children who were prospectively enrolled in studies of chronic cough and had flexible bronchoscopy performed. Recent ß-lactam or macrolide antibiotic use was recorded. M. catarrhalis isolates stored at -80 °C were re-cultured and susceptibility determined to a range of antibiotics including the macrolide antibiotic erythromycin. RESULTS: Data from concurrently collected NP and BAL specimens were available from 547 children (median age 2.4 years) enrolled from 2007 to 2016. M. catarrhalis NP carriage was detected in 149 (27  %) children and lower airway infection (≥104 c.f.u. ml-1 BAL) in 67 (12  %) children. In total, 91  % of 222 M. catarrhalis isolates were ß-lactamase producers, and non-susceptibility was high to benzylpenicillin (98 %), cefaclor (39 %) and cotrimoxazole (38 %). Overall, >97  % isolates were susceptible to cefuroxime, chloramphenicol, erythromycin and tetracycline; three isolates were erythromycin-resistant (MIC >0.5 mg l-1). Recent macrolide antibiotics (n=152 children, 28 %) were associated with significantly reduced M. catarrhalis carriage and lower airway infection episodes compared to children who did not receive macrolides; odds ratios 0.19 (95  % CI 0.10-0.35) and 0.15 (0.04-0.41), respectively. CONCLUSION: Despite the frequent use of macrolides, few macrolide-resistant isolates were detected. This suggests a fitness cost associated with macrolide resistance in M. catarrhalis. Macrolide antibiotics remain an effective choice for treating M. catarrhalis lower airway infection in children with chronic endobronchial suppuration.

Microbiological changes observed over 48 weeks of treatment with inhaled liposomal ciprofloxacin in individuals with non-cystic fibrosis bronchiectasis and chronic Pseudomonas aeruginosa lung infection.

OBJECTIVES: Non-cystic fibrosis bronchiectasis (NCFBE) with Pseudomonas aeruginosa has been associated with increased pulmonary exacerbation (PEx) and mortality risk. European Respiratory Society guidelines conditionally recommend inhaled antimicrobials for persons with NCFBE, P aeruginosa and three or more PEx/year. We report microbiological results of two randomized, 48-week placebo-controlled trials of ARD-3150 (inhaled liposomal ciprofloxacin) in individuals with NCFBE with P aeruginosa and PEx history [Lancet Respir Med 2019;7:213-26]. METHODS: Respiratory secretions from 582 participants receiving up to six 28-day on/off treatment cycles were analysed for sputum P. aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Escherichia coli densities, P. aeruginosa susceptibilities to ciprofloxacin and nine other antimicrobials, and prevalence of other bacterial opportunists. Associations between PEx risk and sputum density, antimicrobial susceptibility and opportunist prevalence changes were studied. RESULTS: Sputum P. aeruginosa density reductions from baseline after ARD-3150 treatments ranged from 1.77 (95% CI 2.13-1.40) versus 0.54 (95% CI 0.89-0.19) log10 CFU/g for placebo (second period) to 2.07 (95% CI 2.45-1.69) versus 0.70 (95% CI 1.11-0.29) log10 CFU/g for placebo (fourth period) with only modest correlation between density reduction magnitude and PEx benefit. ARD-3150 (but not placebo) treatment was associated with increased P. aeruginosa ciprofloxacin MIC but not emergence of other bacterial opportunists across the study; ciprofloxacin MIC50 increased from 0.5 to 1 mg/L, MIC90 increased from 4 to 16 mg/L. Other antimicrobial MIC were mostly unaffected. CONCLUSION: Microbiological changes over 48 weeks of ARD-3150 treatment appear modest. Ciprofloxacin susceptibility (but not other antimicrobial susceptibility) decreases were observed that did not appear to preclude PEx risk reduction benefit.

Spotlight on inhaled ciprofloxacin and its potential in the treatment of non-cystic fibrosis bronchiectasis.

Non-cystic fibrosis bronchiectasis (NCFB) is a severe chronic illness characterized by irreversible dilation of airways and thickening of bronchial walls, chronic inflammation, repeated infections, and progressive obstruction of the airways. In contrast to cystic fibrosis bronchiectasis (CFB), which is a well-defined genetic disorder, NCFB is a heterogeneous disease caused by many different medical entities. Inhaled antibiotics are effective for patients with CFB, but their efficacy in NCFB has not been proven. The main pathogens involved in the colonization of patients with bronchiectasis are Haemophilus influenza, Moraxella catarrhalis, Staphylococcus aureus, and Pseudomonas aeruginosa. The latter is associated with increased morbidity and mortality. In addition, in NCFB, P. aeruginosa strains are frequently more resistant than those in CFB. At present, there are no approved inhaled antibiotic therapies for NCFB patients. Inhaled ciprofloxacin has been under investigation in the last few years. In two phase II randomized, double-blind, placebo-controlled trials, the use of inhaled ciprofloxacin was significantly associated with reduction in sputum bacterial density and greater eradication rates. In four phase III randomized, double-blind, placebo-controlled trials, the results regarding the time of the first exacerbation and the rate of exacerbations were inconsistent. Specifically, ORBIT-4 and RESPIRE-1 trials showed clinical benefit (prolongation of the time of the first exacerbation and reduced rate of exacerbations in the treatment group compared to the placebo group), whereas the ORBIT-3 and RESPIRE-2 failed to achieve their primary endpoints. The RESPIRE-1 was the first trial that examined the 14-days on/off course separate from the standard 28-days on/off regimen, which is based on CFB protocol treatments. The current data on the efficacy of inhaled ciprofloxacin are encouraging, but further evaluation is needed to determine the appropriate target group and the ideal duration of treatment.

Treatment of Mycobacterium avium Complex (MAC).

Mycobacterium avium complex (MAC) is the most commonly isolated nontuberculous mycobacterial respiratory pathogen worldwide. MAC lung disease is manifested either by fibrocavitary radiographic changes similar to pulmonary tuberculosis or by bronchiectasis with nodular and reticulonodular radiographic changes. This latter form of MAC lung disease, termed "nodular bronchiectatic (NB) MAC lung disease" is the most common form of MAC lung disease in the United States. Treatment at the time of diagnosis is always indicated for fibrocavitary MAC lung disease because it is always progressive and associated with increased morbidity and mortality compared with NB MAC lung disease. In contrast, the NB form of MAC lung disease is more indolent and frequently does not require antimycobacterial therapy. For patients with NB MAC lung disease, the priorities are typically to treat the underlying bronchiectasis and determine the course and impact of the MAC infection over time. Guidelines-based MAC therapy with multidrug regimens including macrolides is usually effective, but far from as predictably effective and durable as therapy for tuberculosis. It is imperative that clinicians are familiar with MAC drug resistance mechanisms and the pitfalls of inappropriate dependence on in vitro drug susceptibility testing which can predispose patients to the development of macrolide resistance with its attendant high mortality. It is now more than 20 years since the emergence of macrolides for MAC therapy with no new comparably effective agents introduced in that time, although one new inhaled amikacin therapy under study offers promise.

Dual antibiotics for bronchiectasis.

BACKGROUND: Bronchiectasis is a chronic respiratory disease characterised by abnormal and irreversible dilatation of the smaller airways and associated with a mortality rate greater than twice that of the general population. Antibiotics serve as front-line therapy for managing bacterial load, but their use is weighed against the development of antibiotic resistance. Dual antibiotic therapy has the potential to suppress infection from multiple strains of bacteria, leading to more successful treatment of exacerbations, reduced symptoms, and improved quality of life. Further evidence is required on the efficacy of dual antibiotics in terms of management of exacerbations and extent of antibiotic resistance. OBJECTIVES: To evaluate the effects of dual antibiotics in the treatment of adults and children with bronchiectasis. SEARCH METHODS: We identified studies from the Cochrane Airways Group Specialised Register (CAGR), which includes the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine (AMED), and PsycINFO, as well as studies obtained by handsearching of journals/abstracts. We also searched the following trial registries: US National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform. We imposed no restriction on language of publication. We conducted our search in October 2017. SELECTION CRITERIA: We searched for randomised controlled trials comparing dual antibiotics versus a single antibiotic for short-term (< 4 weeks) or long-term management of bronchiectasis diagnosed in adults and/or children by bronchography, plain film chest radiography, or high-resolution computed tomography. Primary outcomes included exacerbations, length of hospitalisation, and serious adverse events. Secondary outcomes were response rates, emergence of resistance to antibiotics, systemic markers of infection, sputum volume and purulence, measures of lung function, adverse events/effects, deaths, exercise capacity, and health-related quality of life. We did not apply outcome measures as selection criteria. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of 287 records, along with the full text of seven reports. Two studies met review inclusion criteria. Two review authors independently extracted outcome data and assessed risk of bias. We extracted data from only one study and conducted GRADE assessments for the following outcomes: successful treatment of exacerbation; response rates; and serious adverse events. MAIN RESULTS: Two randomised trials assessed the effectiveness of oral plus inhaled dual therapy versus oral monotherapy in a total of 118 adults with a mean age of 62.8 years. One multi-centre trial compared inhaled tobramycin plus oral ciprofloxacin versus ciprofloxacin alone, and one single-centre trial compared nebulised gentamicin plus systemic antibiotics versus a systemic antibiotic alone. Published papers did not report study funding sources.Effect estimates from one small study with 53 adults showed no evidence of treatment benefit with oral plus inhaled dual therapy for the following primary outcomes at the end of the study: successful management of exacerbation - cure at day 42 (odds ratio (OR) 0.66, 95% confidence interval (CI) 0.22 to 2.01; 53 participants; one study; very low-quality evidence); number of participants with Pseudomonas aeruginosa eradication at day 21 (OR 2.33, 95% CI 0.66 to 8.24; 53 participants; one study; very low-quality evidence); and serious adverse events (OR 0.48, 95% CI 0.08 to 2.87; 53 participants; one study; very low-quality evidence). Similarly, researchers provided no evidence of treatment benefit for the following secondary outcomes: clinical response rates - relapse at day 42 (OR 0.57, 95% CI 0.12 to 2.69; 53 participants; one study; very low-quality evidence); microbiological response rate at day 21 - eradicated (OR 2.40, 95% CI 0.67 to 8.65; 53 participants; one study; very low-quality evidence); and adverse events - incidence of wheeze (OR 5.75, 95% CI 1.55 to 21.33). Data show no evidence of benefit in terms of sputum volume, lung function, or antibiotic resistance. Outcomes from a second small study with 65 adults, available only as an abstract, were not included in the quantitative data synthesis. The included studies did not report our other primary outcomes: duration; frequency; and time to next exacerbation; nor our secondary outcomes: systemic markers of infection; exercise capacity; and quality of life. We did not identify any trials that included children. AUTHORS' CONCLUSIONS: A small number of studies in adults have generated high-quality evidence that is insufficient to inform robust conclusions, and studies in children have provided no evidence. We identified only one dual-therapy combination of oral and inhaled antibiotics. Results from this single trial of 53 adults that we were able to include in the quantitative synthesis showed no evidence of treatment benefit with oral plus inhaled dual therapy in terms of successful treatment of exacerbations, serious adverse events, sputum volume, lung function, and antibiotic resistance. Further high-quality research is required to determine the efficacy and safety of other combinations of dual antibiotics for both adults and children with bronchiectasis, particularly in terms of antibiotic resistance.

Antibiotic-resistant Pseudomonas aeruginosa infection in patients with bronchiectasis: prevalence, risk factors and prognostic implications.

Background and aims: Pseudomonas aeruginosa (PA) is the most common pathogen in bronchiectasis and frequently develops resistance to multiple classes of antibiotics, but little is known about the clinical impacts of PA-resistant (PA-R) isolates on bronchiectasis. We, therefore, investigated the prevalence, risk factors and prognostic implications of PA-R isolates in hospitalized bronchiectasis patients. Patients and methods: Between June 2011 and July 2016, data from adult bronchiectasis patients isolated with PA at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. PA was classified as PA-R in case antibiogram demonstrated resistance on at least one occasion. Results: Seven hundred forty-seven bronchiectasis patients were assessed. Of these, 147 (19.7%) had PA isolate in the sputum or bronchoscopic culture. PA-R and PA-sensitive accounted for 88 (59.9%) and 59 (31.1%) patients, respectively. In multivariate model, factors associated with PA-R isolate in bronchiectasis included prior exposure to antibiotics (odds ratio [OR] =6.18), three or more exacerbations in the previous year (OR =2.81), higher modified Medical Research Council dyspnea scores (OR =1.93) and greater radiologic severity (OR =1.15). During follow-up (median: 26 months; interquartile range: 6-59 months), 36 patients died, of whom 24 (66.7%) had PA-R isolate at baseline. However, PA-R isolate was not associated with greater all-cause mortality in bronchiectasis. Conclusion: PA-R infection is common among bronchiectasis patients, mainly determined by prior exposure to antibiotics, frequent exacerbations, more pronounced dyspnea and more severe radiologic involvement. However, PA-R isolate is not an independent risk factor for all-cause mortality in bronchiectasis.

Lobar distribution in non-cystic fibrosis bronchiectasis predicts bacteriologic pathogen treatment.

Non-cystic fibrosis bronchiectasis (NCFBr) is a major cause of morbidity due to frequent infectious exacerbations. We analyzed the influence of patient age and bronchiectasis location on the bacterial profile of patients with NCFBr. This retrospective cohort study included 339 subjects diagnosed with an infectious exacerbation of NCFBr during the 9-year period between January 2006 and December 2014. Bronchoalveolar lavage (BAL) cultures and high-resolution computed tomography scans (HRCT) were utilized to characterize the location of the bronchiectasis and bacteriologic pathogenic profile. In univariate logistic regression, the frequency of Haemophilus influenzae was higher in patients aged ≤64 years (OR = 0.969, p < 0.0001, 95 % CI 0.954-0.983), whereas the frequency of Pseudomonas aeruginosa (OR = 1.027, p = 0.008, 95 % CI 1.007-1.048) and Enterobacteriaceae (OR = 1.039, p = 0.01, 95 % CI 1.009-1.069) were significantly higher in patients aged >64 years. The lobar distribution of bronchiectasis in the subjects was 25.9 % in the right middle lobe (RML), 20.7 % in the right lower lobe (RLL), 20.4 % in the left lower lobe (LLL), 13.8 % in the lingula, 13 % in the right upper lobe (RUL), and 6.2 % in the left upper lobe (LUL). In the lower lobes, H. influenzae was the dominant species isolated, whereas in the RUL it was P. aeruginosa and in the LUL it was non- tuberculous mycobacterium (NTM). H. influenzae was more prevalent in younger patients, whereas P. aeruginosa, Enterobacteriaceae and NTM predominated in older patients. Different pathogens were associated with different lobar distributions. The RML, RLL and LLL showed a greater tendency to develop bronchiectasis than other lobes.

Outcomes of Pseudomonas eradication therapy in patients with non-cystic fibrosis bronchiectasis.

Pseudomonas aeruginosa infection is associated with poorer outcomes in non-cystic fibrosis bronchiectasis. It is unknown whether early eradication improves outcomes. This retrospective study assessed clinical and microbiological outcomes of eradication therapy following initial Pseudomonas infection. All patients undergoing Pseudomonas eradication therapy from 2004 to 2010 were identified retrospectively and assessed for microbiological eradication, exacerbation frequency, hospital admissions, clinical symptoms and lung function. 30 patients were identified with median follow-up time 26.4 months. Eradication therapy involved intravenous antibiotics (n = 12), intravenous antibiotics followed by oral ciprofloxacin (n = 13) or ciprofloxacin alone (n = 5), combined with 3 months of nebulised colistin. Pseudomonas was initially eradicated from sputum in 24 patients (80.0%). 13/24 patients remained Pseudomonas-free and 11/24 were subsequently reinfected (median time 6.2 months). Exacerbation frequency was significantly reduced from 3.93 per year pre-eradication and 2.09 post-eradication (p = 0.002). Admission rates were similar, at 0.39 per year pre-eradication and 0.29 post-eradication (p = NS). 20/30 patients reported initial clinical improvement, whilst at one-year follow up, 19/21 had further improved or remained stable. Lung function was unchanged. This study demonstrates that Pseudomonas can be eradicated from a high proportion of patients, which may lead to prolonged clearance and reduced exacerbation rates. This important outcome requires confirmation in a prospective study.

[Clinical features and treatment history of clarithromycin resistance in M. avium-intracellulare complex pulmonary disease patients].

Effective antimicrobial treatment of Mycobacterium avium-intracellulare complex (MAC) has not been established. Clarithromycin (CAM) is an extremely important drug in treatment regimens of MAC diseases. Except for monotherapy, the clinical features of CAM resistance are not clear. We investigated the clinical background of CAM resistance of pulmonary MAC disease patients. Minimum inhibitory concentrations (MICs) of CAM to 283 strains of M. avium and 58 strains of M. intracellulare were determined by drug susceptibility test using BrothMIC NTM. All 243 M. avium isolates from untreated patients except one isolate were susceptible to CAM. We also examined CAM susceptibility of 40 pulmonary disease patients who received chemotherapy including CAM during a period of over 6 months. Seventeen patients (43%) were resistant to CAM. All (17/17) resistant patients were treated with CAM monotherapy. However 8 of the 23 (35%) susceptible patients were also treated with monotherapy. Many resistant patients were treated with high dose CAM monotherapy and were classified as the non-nodular bronchiectasis type. However 7 of 8 susceptible patients despite long-term monotherapy were the nodular bronchiectasis type. High dose CAM monotherapy and non-nodular bronchiectasis subtype were considered to be risk factors for CAM resistance.

Addition of inhaled tobramycin to ciprofloxacin for acute exacerbations of Pseudomonas aeruginosa infection in adult bronchiectasis.

RATIONALE: Pseudomonas aeruginosa lung infection in patients with bronchiectasis, a chronic airway disease that is characterized by episodes of exacerbation, is associated with more severe disease and a higher utilization of health-care resources. Inhaled tobramycin solution reduces the number of acute exacerbations in patients with cystic fibrosis (CF)-related bronchiectasis with P aeruginosa infection but remains untested in the treatment of exacerbations in patients with non-CF bronchiectasis. OBJECTIVES: This study tested the effect of adding inhaled tobramycin solution to oral ciprofloxacin (Cip) for the treatment of acute exacerbations of non-CF bronchiectasis in patients with P aeruginosa infection. METHODS: A double-blind, randomized, active comparator, parallel-design study conducted at 17 study centers (5 in the United Kingdom, and 12 in the United States) compared 2 weeks of therapy with Cip with either an inhaled tobramycin solution or placebo in 53 adults with known P aeruginosa infection who were having acute exacerbations of bronchiectasis. MEASUREMENTS: Clinical symptoms, pulmonary function, clinical efficacy, and sputum microbiology were investigated prospectively. MAIN RESULTS: An inhaled solution of Cip with tobramycin, compared to placebo, achieved greater microbiological response but no statistically significant difference in clinical efficacy at days 14 or 21. Clinical and microbiological outcomes at the test of cure (ie, the clinical outcome assessment at day 21) were concordant when an inhaled tobramycin solution was added to therapy with Cip and compared to placebo (p = 0.01). Both subject groups had similar overall adverse event rates, but subjects receiving therapy with an inhaled tobramycin solution reported an increased frequency of wheeze (50%; placebo group, 15%). CONCLUSIONS: The addition of an inhaled tobramycin solution to therapy with oral Cip for the treatment of acute exacerbations of bronchiectasis due to P aeruginosa improved microbiological outcome and was concordant with clinical outcome; the inability to demonstrate an additional clinical benefit may have been due to emergent wheeze resulting from treatment.

Failure of systemic antibiotic in preventing sequential endogenous endophthalmitis of a bronchiectasis patient.

PURPOSE: To report a rare presentation of bilateral, sequential Pseudomonas aeruginosa endogenous endophthalmitis in a woman with bronchiectasis. DESIGN: Interventional case report. METHODS: A 69-year-old woman with bronchiectasis developed right and then left endogenous endophthalmitis with the microbial of P. aeruginosa, even though a course of 3-week intravenous ceftazidime antibiotic was prescribed. RESULTS: The presentation of endogenous endophthalmitis in the right eye was late, and final visual acuity was hand movements. The condition was recognized much earlier in the left eye, and the infection was treated early on with vitrectomy and intravitreal antibiotics. Visual acuity at 1 year was stable at 20/40. CONCLUSION: Systemic antibiotic failed to eradicate the primary source of Pseudomonas infection in the bronchiectasis patient. Unusual, painful red eye may be the presenting feature of endogenous endophthalmitis. Early vitrectomy may be considered in endogenous endophthalmitis caused by virulent pathogens such P. aeruginosa.

Genetic characterization of fluoroquinolone-resistant Streptococcus pneumoniae strains isolated during ciprofloxacin therapy from a patient with bronchiectasis.

Five Spain(9V-3) Streptococcus pneumoniae strains were isolated from a patient with bronchiectasis who had received long-term ciprofloxacin therapy. One ciprofloxacin-susceptible strain was isolated before treatment, and four ciprofloxacin-resistant strains were isolated during treatment. The resistant strains were derived from the susceptible strain either by a parC mutation (low-level resistance) or by parC and gyrA mutations (high-level resistance). This study shows that ciprofloxacin therapy in a patient colonized by susceptible S. pneumoniae may select fluoroquinolone-resistant mutants.

[Effects of the zhikuofang on the inflammation and cytostatics of the airway model of bronchiectasis].

OBJECTIVE: To explore the effects of Zhikuofang, a TCM prescription, and Ofloxacin on the inflammation and cytostatics of the airway model of bronchiectasis. METHOD: The airway model of bronchiectasis (AMB) was set up and infused with Ps. Aeruginosa. A comparison between the effects of Zhikuofang and Of loxacin on the AMB was made. RESULT: Zhikuofang is better than Ofloxacin in following aspects: lowering the density of inflammation cells in blood, decreasing the volume of tracheal secretion and inhibiting the cytostatics (IL-8 and TNF-alpha) of the trachea tissue, but Ofloxacin is more effective in diminishing the amount of bacteria in trachea flushing liquor. There was no marked difference between them in their histopathy effects on the trachea. CONCLUSION: Zhikuofang probably plays antiphlogistic and bacteriostatic effects by inhibiting the IL-8 and TNF-alpha, resisting secretion, decreasing the inflammation cells and resisting inflammation of trachea.

Treatment With tobramycin solution for inhalation in bronchiectasis patients with Pseudomonas aeruginosa.

A randomized, placebo-controlled, multicenter trial evaluated the safety and efficacy of 300 mg aerosolized tobramycin solution for inhalation (TSI) administered twice daily for 4 weeks in 74 bronchiectasis patients colonized with Pseudomonas aeruginosa (PA). Patients were evenly divided between TSI therapy and placebo. After 2 weeks of treatment, patients treated with TSI had a mean reduction in sputum PA density of 4.8 log(10.) This reduction was maintained for the duration of treatment. The placebo group showed no change in PA density during the study. Two weeks after the end of therapy, PA had been eradicated in 13 TSI-treated patients. PA was not eradicated in any placebo patients. Among those colonized with Staphylococcus aureus at baseline, 6 of 9 patients in the TSI group and 2 of 9 patients in the placebo group were culture negative for this organism 2 weeks posttreatment. Sixty-two percent of TSI-treated patients were judged by a physician as having an improved general health status, compared with 38% of placebo-treated patients. Dyspnea, wheezing, and chest tightness were reported more frequently in the TSI-treated patient group than in the placebo-treated patient group.

Efficacy and safety of long-term ciprofloxacin in the management of severe bronchiectasis.

The efficacy and safety of long-term ciprofloxacin therapy in the management of severe bronchiectasis were retrospectively assessed in patients who had taken oral ciprofloxacin continuously for at least 90 days. The drug was well tolerated, with only one reported side effect. Treatment resulted in a symptomatic improvement in seven of the ten patients and significant improvements in peak expiratory flow rate and residual volume. There was a decrease in the number of infective exacerbations from 6.2 +/- 2.9 during 365 days to 0.5 +/- 0.53 during 412 days. Resistance to ciprofloxacin developed in 2 patients with Pseudomonas aeruginosa infection and this was associated with clinical deterioration, but in a further two patients with P. aeruginosa the pathogen was eradicated. Two patients had persistent Streptococcus pneumoniae cultured from sputum but this was not associated with clinical deterioration. The study suggests that ciprofloxacin is effective and safe in the long-term treatment of chronic bronchial sepsis due to bronchiectasis, but emergence of P. aeruginosa resistance is of some concern.