Comprehensive Care Management in Conjunction with Sputum Cytometry-Guided Pharmacotherapy in a Post-Discharge Clinic for Patients with COPD.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are amongst the most common reasons for hospital admission, and recurrent episodes occur frequently. Comprehensive care management (CCM) strategies have modest effect in preventing re-admissions. The objectives of this study were to examine the utility of optimizing anti-inflammatory therapy guided by sputum cytometry in the post-hospitalization setting, and to assess the feasibility and effectiveness of a clinic combining CCM and sputum-guided therapy. This is an observational study examining patients who received open-label CCM and sputum cytometry-guided pharmacotherapy in a COPD post-discharge clinic. Referral was based on high risk for readmission after hospitalization for AECOPD. The primary outcome was the change in COPD-related healthcare utilization before and after Visit 1, and this was analyzed with a mixed-effects negative binomial model controlling for age, number of follow-up clinic visits, pack years, current smoking and FEV1. Of 138 patients referred to the clinic, 73% attended at least one visit. Mean FEV1 was 42.8 (19.3) % predicted. Of the patients attending clinic, 42.6% produced an adequate sputum sample, and 32.7% had an abnormal sputum. By individual, infectious bronchitis was the most common (25.7%), followed by eosinophilic bronchitis (13.9%). Comparing the 6-months prior to and after the first clinic visit, there was a lower incidence rate ratio after visit 1 for COPD-related healthcare utilization (0.26 (95%CI 0.22,0.33; p < 0.001)). A COPD post-discharge clinic combining sputum-guided treatment and CCM was feasible and associated with a nearly 75% reduction in the incidence of COPD-related healthcare utilization.

[Criteria for treating MRSA in sputum]. / Kriterien zur Behandlung von MRSA im Sputum?

Methicillin-resistant strains of Staphylococcus aureus (MRSA) are of particular significance for the management of patients with airway infections, since the disease course is often complicated and treatment rendered difficult by multiple resistance. Their prevalence is now slowly declining, but still alarmingly high. Hospital-acquired infections are predominant, but hospital-associated and community-acquired infections do occur, as do rare infections with livestock-acquired strains. Non-nosocomial strains are characterized by different pathogenic factors and a different spectrum of antibacterial resistance; they often have a threatening disease course. Anti-infectives with activity against MRSA are unusual and have particular toxicity profiles. On the other hand, MRSA colonization is eliminated spontaneously in healthy people and acute bronchitis is treatable by common oral antibiotics. However, chronic airway infection in bronchiectasis and other forms of structural airway damage requires a complex systemic and local treatment approach for pathogen elimination.

Update on Pediatric Cough.

Despite the high prevalence of cough in children, the topic has been poorly researched. Although pediatricians recognize that chronic cough in children is different from that in adults, this difference seems less recognizable to other health professionals. During childhood, the respiratory tract and nervous system undergo a series of anatomical and physiological maturation processes that influence the cough reflex. Additionally, immunological responses undergo developmental and memorial processes that make infection and congenital abnormalities the overwhelming cause of cough in children. The lack of comprehensive clinical data regarding chronic cough in children has initially required pediatricians to adopt an adult approach to the problem. In the last 10 years, however, research has led to the reconsideration of the etiology of chronic cough in children. Currently, attention has focused on protracted bacterial bronchitis as a major cause of chronic cough in preschool-aged children and as a possible precursor of bronchiectasis. New research horizons are emerging for both the treatment and prevention of particular causes of chronic cough in children.

Helicobacter pylori infection and respiratory diseases: actual data and directions for future studies.

Helicobacter pylori (H. pylori) has been conclusively related to several gastroduodenal diseases. The possible role of the bacterium in the development of extragastric manifestations has been investigated in the past few years. To identify all publications on the association between H. pylori and respiratory diseases, a MEDLINE search of all studies published in English from 1965 to 2013 was conducted. All data are based on case-control studies. Controversial findings of H. pylori seroprevalence have been obtained in patients with bronchial asthma, lung cancer, pulmonary tuberculosis, sarcoidosis, cystic fibrosis, chronic bronchitis and bronchiectasis. At present, on epidemiological bases, there is no definite evidence of a causal relationship between H. pylori infection and respiratory diseases. There is a low consideration of confounding factors as poorer socioeconomic status and tobacco use. The activation of pro-inflammatory cytokines by H. pylori might be a possible pathogenetic mechanism. However, there are no convincing data about the influence of H. pylori on the inflammatory changes of the bronchoepithelium so far. Further studies are needed on the impact of H. pylori eradication, on the prevention, development and natural history of these disorders.

Sputum colour and bacteria in chronic bronchitis exacerbations: a pooled analysis.

We examined the correlation between sputum colour and the presence of potentially pathogenic bacteria in acute exacerbations of chronic bronchitis (AECBs). Data were pooled from six multicentre studies comparing moxifloxacin with other antimicrobials in patients with an AECB. Sputum was collected before antimicrobial therapy, and bacteria were identified by culture and Gram staining. Association between sputum colour and bacteria was determined using logistic regression. Of 4,089 sputum samples, a colour was reported in 4,003; 1,898 (46.4%) were culture-positive. Green or yellow sputum samples were most likely to yield bacteria (58.9% and 45.5% of samples, respectively), compared with 18% of clear and 39% of rust-coloured samples positive for potentially pathogenic microorganisms. Factors predicting a positive culture were sputum colour (the strongest predictor), sputum purulence, increased dyspnoea, male sex and absence of fever. Green or yellow versus white sputum colour was associated with a sensitivity of 94.7% and a specificity of 15% for the presence of bacteria. Sputum colour, particularly green and yellow, was a stronger predictor of potentially pathogenic bacteria than sputum purulence and increased dyspnoea in AECB patients. However, it does not necessarily predict the need for antibiotic treatment in all patients with AECB.

Protocol for CLASSIC PBB: comparison of lower airway sampling strategies in children with protracted bacterial bronchitis.

BACKGROUND: Protracted bacterial bronchitis (PBB) is an endobronchial infection and a the most common cause of chronic wet cough in young children. It is treated with antibiotics, which can only be targeted if the causative organism is known. As most affected children do not expectorate sputum, lower airway samples can only be obtained by bronchoalveolar lavage (BAL) samples taken during flexible bronchoscopy (FB-BAL). This is invasive and is therefore reserved for children with severe or relapsing cases. Most children with PBB are treated empirically with broad spectrum antibiotics. CLASSIC PBB will compare the pathogen yield from two less invasive strategies with that from FB-BAL to see if they are comparable. METHODS: 131 children with PBB from four UK centres referred FB-BAL will be recruited. When attending for FB-BAL, they will have a cough swab and an induced sputum sample obtained. The primary outcome will be the discordance of the pathogen yield from the cough swab and the induced sputum when compared with FB-BAL. Secondary outcomes will be the sensitivity of each sampling strategy, the success rate of the induced sputum in producing a usable sample and the tolerability of each of the three sampling strategies. DISCUSSION: If either or both of the two less invasive airway sampling strategies are shown to be a useful alternative to FB-BAL, this will lead to more children with PBB having lower airway samples enabling targeted antibiotic prescribing. It would also reduce the need for FB, which is known to be burdensome for children and their families. TRIAL REGISTRATION NUMBER: ISRCTN79883982.

A multicentre surveillance study on the characteristics, bacterial aetiologies and in vitro antibiotic susceptibilities in patients with acute exacerbations of chronic bronchitis.

BACKGROUND AND OBJECTIVE: Antimicrobial resistance is a global problem and the prevalence is high in many Asian countries. METHODS: A prospective observational study of the prevalence of bacterial pathogens and their antimicrobial susceptibilities in patients with acute exacerbations of chronic bronchitis (AECB) was conducted in Indonesia, Philippines, Korea, Thailand, Malaysia, Taiwan and Hong Kong from August 2006 to April 2008. The diagnosis of AECB was based on increased cough and worsening of two of following: dyspnoea, increased sputum volume or purulence. Patients who had taken antibiotics within 72 h of presentation were excluded. All bacterial strains were submitted to a central laboratory for re-identification and antimicrobial susceptibility testing to 16 antimicrobial agents according to Clinical and Laboratory Standards Institute. RESULTS: Four hundred and seven isolates were identified among 447 patients of AECB. The most frequent organisms isolated were Klebsiella pneumoniae and associated species (n = 91 + 17), Haemophilus influenzae (n = 71), Pseudomonas aeruginosa (n = 63), Streptococcus pneumoniae (n = 32), Acinetobacter baumannii (n = 22) and Moraxella catarrhalis (n = 21). According to Clinical and Laboratory Standards Institute susceptibility breakpoints, 85.7% and >90% of these pathogens were susceptible to levofloxacin and cefepime respectively. Other options with overall lower susceptibilities include imipenem, ceftazidime, ceftriaxone and amoxicillin/clavulanate. CONCLUSIONS: Gram-negative bacteria including Klebsiella spp., P. aeruginosa and Acinetobacter spp. constitute a large proportion of pathogens identified in patients with AECB in some Asian countries. Surveillance on the local prevalence and antibiotic resistance of these organisms is important in guiding appropriate choice of antimicrobials in the management of AECB.

Isolation of nocobactin NAs as Notch signal inhibitors from Nocardia farcinica, a possibility of invasive evolution.

Notch signaling inhibitors with the potential of immune suppressor production by pathogenic bacteria for easy host infection were searched from extracts of Nocardia sp. Nocobactin NA-a (compound 1) and nocobactin NA-b (compound 2), which have been suggested as pathogenesis factors, were isolated from N. farcinica IFM 11523 isolated from the sputum of a Japanese patient with chronic bronchitis. Compounds 1 and 2 showed Notch inhibitory activities with IC50 values of 12.4 and 17.6 µM, respectively. Compound 1 and 2 decreased of Notch1 protein, Notch intracellular domain, and hairy and enhancer of split 1, which is a Notch signaling target protein. In addition, compounds 1 and 2 showed cytotoxicity against mouse macrophage-like cell line RAW264.7 with IC50 values of 18.9 and 21.1 µM, respectively. These results suggested that the Notch inhibitors production by pathogenic bacteria may increase pathogen infectivity.

A novel Filobacterium sp can cause chronic bronchitis in cats.

BACKGROUND: Cilia-associated respiratory bacillus (CARB; now known as Filobacterium rodentium gen. nov., sp. nov.) is a primary pathogen of rodents. A CARB-like organism was reported in post-mortem lung samples of cats using light and electron microscopy. Here we explore by molecular procedures if a Filobacterium sp. is a part of the normal feline lower respiratory microbiome and whether it could in some cats contribute to the development of chronic bronchial disease. METHODOLOGY: A Filobacterium sp. was identified in three Czech cats clinically diagnosed as having chronic neutrophilic bronchitis. Bronchoalveolar lavage fluid (BALF) specimens obtained from these cats were subjected to panbacterial 16S rDNA PCR followed by Sanger sequencing of the V5 to V8 region. After these cats were treated with specific antimicrobials, their clinical signs resolved promptly, without recurrence. Next, BALF specimens from 13 Australian and 11 Italian cats with lower respiratory disease and an additional 16 lung samples of Italian cats who died of various causes were examined using next generation sequencing (NGS). Subsequently, a Filobacterium-specific qPCR assay was developed and used to re-test BALF specimens from the 11 Italian cats and lung tissue homogenates from the additional 16 deceased cats. PRINCIPAL FINDINGS: An amplicon of 548 bp with 91.24% sequence agreement with Filobacterium rodentium was obtained from all three patients, suggesting the novel Filobacterium sp. was the cause of their lower respiratory disease. The novel Filobacterium sp., which we propose to call F. felis, was detected in 3/3 Czech cats with chronic neutrophilic bronchitis, 13/13 Australian cats and 6/11 Italian cats with chronic lower respiratory disease, and 14/16 necropsy lung specimens from Italian cats. NGS and qPCR results all showed identical sequences. The Filobacterium sp. was sometimes the preponderant bacterial species in BALF specimens from cats with lower airway disease. There was an association between the presence of large numbers (greater than 105 organisms/mL) of Filobacterium and the presence of neutrophilic and/or histiocytic inflammation, although only a subset of inflammatory BALF specimens had F. felis as the preponderant organism. CONCLUSION: The novel Filobacterium sp. comprises a finite part of the normal feline lower respiratory microbiome. Under certain circumstances it can increase in absolute and relative abundance and give rise to neutrophilic and/or histiocytic bronchitis, bronchiolitis and bronchopneumonia. These findings strongly suggest that F. felis could be an underdiagnosed cause of feline bronchial disease.

High frequency of ß-lactamase-negative, ampicillin-resistant strains of Haemophilus influenzae in patients with chronic bronchitis in Japan.

In Japan, the increasing incidence of ß-lactum-resistant Haemophilus influenzae infections is of growing concern. We retrospectively studied whether the prevalence of ß-lactamase-negative ampicillin-resistant strains of H. influenzae was influenced by chronic lung diseases. H. influenzae isolates, obtained from patients who were diagnosed with acute or chronic bronchitis, or acute exacerbation of chronic bronchitis in 2005, were studied. In addition to susceptibility testing, polymerase chain reaction (PCR) was performed for the detection of TEM-1 ß-lactamase, and Asn526-Lys and Ser385-Thr amino acid substitutions in the ftsI gene encoding penicillin-binding protein-3 (PBP-3). The minimum inhibitory concentration values of ß-lactams were found to be increased in isolates from patients with chronic bronchitis who had been repeatedly administered antibiotics. Genetic analysis using PCR suggested that this might be associated with a high frequency of ß-lactamase-negative strains with mutations in PBP-3. The presence of ß-lactum-resistant strains needs to be considered for patients with chronic bronchitis in whom H. influenzae is isolated as a causative pathogen.

[Colonization resistance and immunological reactivity of children's oropharyngeal mucosa in health and bronchopulmonary pathology].

The study group was comprised of 27 practically healthy children, 51 patients with acute bronchitis, 15 with chronic bronchitis and 11 with pneumonia. It was shown that changes of microbiocoenosis in back of the throat (BOT) were related to increased mucosal contamination with normal microflora and opportunistic microorganisms. The highest degree of contamination was observed in children with acute bronchitis. Normocoenosis was detected only in 13 practically healthy children. The disorders of microbiocoenosis took the form of disbiosis and acute inflammatory processes in patients with acute and chronic bronchitis and pneumonia. However, the large amount of normal flora together with the high Ig level ensured marked colonization resistance as evidenced by the values of natural colonization coefficient of nasopharyngeal epithelium (NCCNE) and balance coefficient (BC). These data suggested development of compensated secondary immunodeficiencies. In patients with acute bronchitis and pneumonia, local synthesis of Ig prevailed. It is shown that BC can be used to screen children for disorders of mucosal immunity. The presence of increased saliva IgE levels in patients with acute and chronic bronchitis supports the generally accepted concept of bronchi as a "shock organ" in allergic condition. It was demonstrated that IgE levels in saliva increase earlier than in serum and may be used as a prognostic criterion in patients with bronchopulmonary pathology.

Respiratory dysbiosis and population-wide temporal dynamics in canine chronic bronchitis and non-inflammatory respiratory disease.

The lungs of people and companion animals are now recognized to harbor diverse, low biomass bacterial communities. While these communities are difficult to characterize using culture-based approaches, targeted molecular methods such as 16S rRNA amplicon sequencing can do so using DNA extracted from samples such as bronchoalveolar lavage fluid (BALF). Previous studies identified a surprisingly uniform composition of the microbiota in the lungs of healthy research dogs living in a controlled environment, however there are no reports of the lung microbiota of client-owned dogs. Moreover, compositional changes in the lung microbiota depending on disease status have been reported in people, suggesting that similar events may occur in dogs, a species subject to several respiratory disease mechanisms analogous to those seen in people. To address these knowledge gaps, BALF samples from client-owned dogs presenting to the University of Missouri Veterinary Health Center for respiratory signs between 2014 and 2017 were processed for and subjected to 16S rRNA sequencing. Based on specific diagnostic criteria, dogs were categorized as Chronic Bronchitis (CB, n = 53) or non-CB (n = 11). Community structure was compared between groups, as well as to historical data from healthy research dogs (n = 16) of a uniform breed and environment. The lung microbiota detected in all client-owned dogs was markedly different in composition from that previously detected in research dogs and contained increased relative abundance of multiple canine fecal and environmental bacteria, likely due to aspiration associated with their clinical signs. While inter-sample diversity differed significantly between samples from CB and non-CB dogs, the variability within both groups made it difficult to discern reproducible bacterial classifiers of disease. During subsequent analyses to identify other sources of variability within the data however, population-wide temporal dynamics in community structure were observed, with substantial changes occurring in late 2015 and again in early 2017. A review of regional climate data indicated that the first change occurred during a historically warm and wet period, suggesting that changes in environmental conditions may be associated with changes in the respiratory microbiota in the context of respiratory disease. As the lung microbiota in humans and other animals is believed to result from repetitive micro-aspirations during health and in certain disease states associated with dyspnea and laryngeal dysfunction, these data support the increased colonization of the lower airways during compromised airway function, and the potential for temporal effects due to putative factors such as climate.

Duration of initial antibiotic course is associated with recurrent relapse in protracted bacterial bronchitis.

Protracted bacterial bronchitis (PBB) is the leading cause of chronic wet cough in young children from developed countries. Despite its high prevalence there is a paucity of evidence to inform the optimal duration of treatment leading to variation in practice. Relapse of chronic cough is common and recurrent PBB (>3 episodes in 12 months) is associated with a future diagnosis of bronchiectasis. We investigated the factors associated with any relapse (≥1 episode in 12 months) and recurrent PBB in 66 children. No factor was significantly associated with any relapse. Duration of initial antibiotic treatment was the only factor significantly associated with recurrent PBB. Those who received antibiotics for 6 weeks antibiotics were less likely to develop recurrent PBB than those who received for 2 weeks (p=0.046). This is the first study to show an association between duration of initial antibiotic course and therefore future bronchiectasis. Prospective studies are needed to investigate this association.

A disease model descriptive of progression between chronic obstructive pulmonary disease exacerbations and community-acquired pneumonia: roles for underlying lung disease and the pharmacokinetics/pharmacodynamics of the antibiotic.

Patients with chronic obstructive pulmonary disease (COPD) may progress to community-acquired pneumonia (CAP), but there has been no formal study of the factors responsible. We studied the influence of severity of underlying lung disease, pathogen characteristics and the ratio of the area under the concentration-time curve from 0-24h to minimum inhibitory concentration (AUC24/MIC), i.e. the area under the inhibitory curve (AUIC), during the progression from acute exacerbation of chronic bronchitis (AECB) in COPD to CAP. The model parameters were derived from a multinational database of 3885 patients with AECB or CAP (April 1996 to July 2006). Patients with underlying COPD were evaluated in two separate analyses: infection progression between COPD and CAP within Global Initiative for Chronic Obstructive Lung Disease (GOLD)-like grouping (GLG); and distribution of pathogen by GLG, CAP and AECB. Secondary analyses examined the impact of target AUIC attainment on progression to CAP for Streptococcus pneumoniae. The relative impact of GLG and AUIC were modelled in multivariate logistic regression for S. pneumoniae. Progression to CAP linked directly with GLG I/II, III and IV (18.3%, 31.7% and 48.9%, respectively; P < 0.001). Progression to CAP was strongly associated with S. pneumoniae (57.3%), whilst other pathogens were predominant in AECB that did not progress to CAP (61.7%) (P = 0.002). AUIC > or = 100 was associated with AECB (65.1%) and AUIC < 100 with CAP (91.7%) (P < 0.001). In conclusion, the frequency of progression to CAP increases directly with GLG. For S. pneumoniae, achieving an AUIC > or =100 can attenuate progression, regardless of GLG. Thus, AUIC > or = 100 appears to be a viable antibiotic selection strategy to protect patients with S. pneumoniae from developing CAP.

Asthma and protracted bronchitis: who fares better during an acute respiratory infection?

AIM: Acute respiratory infections (ARI) are common in children, and symptoms range from days to weeks. The aim of this study was to determine if children with asthma have more severe ARI episodes compared with children with protracted bronchitis and controls. METHODS: Parents prospectively scored their child's next ARI using the Canadian acute respiratory illness and flu scale (CARIFS) and a validated cough diary (on days 1-7, 10 and 14 of illness). Children were age- and season-matched. RESULTS: On days 10 and 14 of illness, children with protracted bronchitis had significantly higher median CARIFS when compared with children with asthma and healthy controls. On day 14, the median CARIFS were: asthma = 4.1 (interquartile range (IQR) 4.0), protracted bronchitis = 19.6 (IQR 25.8) and controls = 4.1 (IQR 5.25). The median cough score was significantly different between groups on days 1, 7, 10 and 14 (P < 0.001). A significantly higher proportion of children with protracted bronchitis (63%) were still coughing at day 14 in comparison with children with asthma (24%) and healthy controls (26%). CONCLUSION: Children with protracted bronchitis had the most severe ARI symptoms and higher percentage of respiratory morbidity at day 14 in comparison with children with asthma and healthy controls.

[Resistance by hypermutable Pseudomonas aeruginosa and beta-lactamases production].

OBJECTIVE: To determine the relation between resistance of hypermutable Pseudomonas aeruginosa and beta-lactamases produced. METHODS: The bacteria cultured were identified with API 20NE system. Susceptibilities of the bacteria were detected by disk diffusion method. The hypermutable strains were tested with broth dilution assays. The beta-lactamases produced by these strains were characterized by 3-dimensional test and 2-mercaptopropanoic acid inhibited assays. RESULTS: Altogether 120 strains were analyzed and 45 (37.5%) trains were hypermutable.The resistant rates of hypermutable strains were close to or above 60.0% for imipenem, meropenem, cefoperazone/sulbactam, piperacillin/ tazobactam, ceftazidime, cephfime, aztreonam, amikacin and ciprofloxacin.The 3-dimensional test showed that 18 (40.0%) strains produced extended spectrum beta-lactamases (ESBLs), 25 (55.6%) strains produced AmpC enzymes, and 6 (13.3%) strains produced metallo-beta-lactamases. CONCLUSION: The resistant rates of hypermutablce strains of Pseudomonas aeruginosa to routine antibiotics are high, which is one of the most important reasons for multi-drug resistance that the hypermutable strains produced ESBLs, AmpC enzymes, and metallo-beta-lactamases.

Multiple Respiratory Microbiota Profiles Are Associated With Lower Airway Inflammation in Children With Protracted Bacterial Bronchitis.

BACKGROUND: Effective management of protracted bacterial bronchitis (PBB) is needed to prevent chronic disease (eg, bronchiectasis). Understanding the contributions of ongoing airway infection and inflammation is important to achieving optimal PBB treatments. The aim of this study was to compare BAL microbiota, bacterial biomass, and inflammatory markers in children with PBB and age-matched control patients. METHODS: BAL was prospectively collected from 28 children with PBB (median age, 1.7 years; range, 0.6-7.4) and 8 control patients (median age, 1.9 years; range, 0.4-4.7). BAL microbiology was determined using culture, 16S ribosomal RNA gene sequencing and bacterial biomass quantification. BAL inflammatory cells, IL-8, and IL-1ß were used to assess lower airway inflammation. RESULTS: Bacterial biomass, neutrophil percentage, IL-8, and IL-1ß levels were significantly higher in children with PBB compared with control patients. BAL microbiota in children with PBB was significantly different to that of control patients (permutational multivariate analysis of variance P = .001) and clustered into four distinct profiles that were either dominated by a respiratory pathogen or contained a more diverse microbiota including Prevotella species. Alpha diversity was unrelated to bacterial biomass, culture of recognized respiratory pathogens, or inflammatory markers. CONCLUSIONS: Neutrophilic inflammation in children with PBB was associated with multiple BAL microbiota profiles. Significant associations between inflammatory markers and bacterial biomass, but not alpha diversity, suggest that inflammation in children with PBB is not driven by single pathogenic species. Understanding the role of the entire respiratory microbiota in PBB pathogenesis may be important to determining whether bacteria other than the recognized pathogens contribute to disease recurrence and progression to bronchiectasis.

Short- versus long-duration antimicrobial treatment for exacerbations of chronic bronchitis: a meta-analysis.

OBJECTIVES: The aim of this study was to evaluate the comparative effectiveness and safety of short (5 days) and long (7 or 10 days) duration antimicrobial treatment of patients with acute exacerbations of chronic bronchitis (AECB). METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) comparing regimens of the same antibiotic (same dosage and same route of administration) administered for a different time period. We searched PubMed, the Cochrane Central Register of Controlled Trials and reference lists from publications, with no language restrictions. RESULTS: Of the 1031 reports retrieved initially, seven RCTs, enrolling 3083 patients with AECB, met our inclusion criteria. The antimicrobials studied in these seven RCTs were quinolones, cefixime and clarithromycin. There was no difference between the short- and long-duration therapies with regard to treatment success in intention-to-treat [relative risk (RR) = 0.99, 95% confidence interval (CI) 0.95-1.03], clinically evaluable (RR = 0.99, 95% CI 0.96-1.02) or microbiologically evaluable (RR = 0.98, 95% CI 0.93-1.02) patients. Short-duration treatment, when compared with long, was associated with fewer adverse events (RR = 0.84, 95% CI 0.72-0.97). CONCLUSIONS: Short-duration treatment seems to be as effective as and safer than long-duration antimicrobial treatment of patients with AECB. Additional research is required to clarify the long-term outcomes (namely the exacerbation-free interval after the resolution of an initial episode) of the compared regimens.

Detection of specific bacterial agents by quantitative PCR assays in the bronchoalveolar lavage fluid of dogs with eosinophilic bronchopneumopathy vs. dogs with chronic bronchitis and healthy dogs.

In humans, Mycoplasma pneumoniae and Bordetella pertussis infections are suggested to trigger or exacerbate asthma. Whether Mycoplasma or Bordetella are associated with chronic inflammatory bronchial diseases in dogs has not been investigated. The aim of this study was to assess detection rates of Mycoplasma canis (M. canis), M. cynos and Bordetella bronchiseptica (Bb), in dogs with eosinophilic bronchopneumopathy (EBP) and chronic bronchitis (CB), compared with healthy dogs. Specific quantitative PCR (qPCR) analysis for M. canis, M. cynos and Bb were retrospectively performed on bronchoalveolar lavage fluid (BALF) collected from 24 dogs with EBP, 21 dogs with CB and 15 healthy dogs. Possible associations between qPCR results and age, BALF cytology or clinical severity scores (CSS) in dogs with EBP were investigated. There was no difference in M. canis, M. cynos and Bb detection rates in dogs with EBP (n=6, n=2 and n=6, respectively) and dogs with CB (n=2, n=2 and n=2, respectively) compared with control dogs (n=4, n=2 and n=2, respectively). In dogs with EBP, the proportion that were qPCR-positive for Bb was higher in dogs with higher CSS (P=0.014) and BALF from Bb-positive dogs had higher percentage of neutrophils (P<0.001). Among dogs that were qPCR-positive for Bb, moderate to high loads were only detected in dogs with EBP. M. canis and M. cynos detection was not associated with EBP or CB; higher Bb loads were only present in dogs with EBP and high CSS. A possible cause and effect relationship between Bb infection or load and EBP remains unclear and requires further investigation.

Role of oral extended-spectrum cephems in the treatment of acute exacerbation of chronic bronchitis.

Risk stratification is the recommended approach for treatment of acute exacerbation of chronic bronchitis (AECB) to optimize the chances of clinical success. The suggested oral therapy for "simple or uncomplicated" AECB, which is predominantly a result of infection due to Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, includes advanced macrolides and 2nd- or 3rd-generation cephalosporins, in addition to the older 1st-line agents (aminopenicillins, doxycycline, trimethoprim/sulfamethoxazole, and erythromycin). In light of increasing resistance of H. influenzae and S. pneumoniae to the older agents, the specific directed structural modification of the cephalosporin nucleus resulted in the development of extended-spectrum 3rd-generation oral cephems with enhanced beta-lactamase stability and improved activity against Gram-positive pathogens (penicillin-susceptible S. pneumoniae and oxacillin-susceptible Staphylococcus aureus). Analysis of results of double-blind randomized clinical trials assessing efficacy of the extended-spectrum oral cephems published since 2000 demonstrates that both cefdinir and cefditoren have similar point estimates of success in comparison to their comparators (cefuroxime, cefprozil, or Locarbacef), when either the clinical cure or the bacteriologic response was analyzed. Thus, oral extended-spectrum 3rd-generation cephems, which retain antimicrobial efficacy against the traditional respiratory pathogens despite changing resistance patterns, offer excellent coverage against the key pathogens involved in simple or uncomplicated AECB.