Antibody response against Mycobacterium avium complex in cystic fibrosis patients measured by a novel IgG ELISA test.

BACKGROUND: Early signs of Mycobacterium avium complex pulmonary disease can be missed in patients with cystic fibrosis due to subclinical infection or delays in mycobacterial culture. The aim of this study was to determine the diagnostic accuracy of a novel enzyme linked immunosorbent assay for immunoglobulin G against Mycobacterium avium complex, which could help stratify patients according to risk. METHODS: A retrospective cross sectional analysis of serum samples from the Copenhagen Cystic Fibrosis Center was performed. Corresponding clinical data were reviewed and patients with cystic fibrosis were assigned to one of four groups based on their mycobacterial culture results. In addition, anti-Mycobacterium avium complex immunoglobulin G levels were measured longitudinally before and after first positive culture in the period 1984-2015. RESULTS: Three-hundred and five patients with cystic fibrosis were included with a median of five nontuberculous mycobacterial cultures. Four individuals had Mycobacterium avium complex pulmonary disease at the time of cross sectional testing and their median antibody level was 22-fold higher than patients with no history of infection (1820 vs. 80 IgG units; p < 0.001). Test sensitivity was 100% (95% CI 40-100) and specificity 77% (95% CI 72-81). Longitudinal kinetics showed rising antibodies prior to first positive culture suggesting diagnostic delay. CONCLUSIONS: Antibody screening for Mycobacterium avium complex may be used as a supplement to culture. Although confirmation in a larger cohort is needed, our findings suggest that stratifying a cystic fibrosis population into high- and low-risk groups based on antibody levels may help clinicians identify patients in need of more frequent culture.

Improving antibiotic treatment of bacterial biofilm by hyperbaric oxygen therapy: Not just hot air.

Bacteria and fungi show substantial increased recalcitrance when growing as infectious biofilms. Chronic infections caused by biofilm growing microorganisms is considered a major problem of modern medicine. New strategies are needed to improve antibiotic treatment of biofilms. We have improved antibiotic treatment of bacterial biofilms by reviving the dormant bacteria and thereby make them susceptible to antibiotics by means of reoxygenation. Here we review the rationale for associating lack of oxygen with low susceptibility in infectious biofilm, and how hyperbaric oxygen therapy may result in reoxygenation leading to enhanced bactericidal activity of antibiotics. We address issues of feasibility and potential adverse effects regarding patient safety and development of resistance. Finally, we propose means for supplying reoxygenation to antibiotic treatment of infectious biofilm with the potential to benefit large groups of patients.

The accessibility of topical treatment in the paranasal sinuses on operated cystic fibrosis patients assessed by scintigraphy.

BACKGROUND: Nasal irrigations with antibiotics are used to eradicate Pseudomonas aeruginosa from the upper airways in patients with cystic fibrosis (CF) and thereby avoid lung colonisations; nevertheless, the efficacy is uncertain. METHODOLOGY: The aim of this study was to investigate the accessibility and durability of solutions in the sinuses before and after sinus surgery. The participants irrigated their noses with radioactively marked saline and were evaluated using a dynamic SPECT/CT scan. The preoperative and postoperative (after 30 days) examinations were compared. RESULTS: Twelve CF patients were included. In 10 out of the 24 scanned maxillary sinuses an improvement was seen postoperatively compared with the preoperative fluid volume. Notably, in 7 out of the 24 sinuses the mucosa was so swollen postoperatively that no fluid was detected. Ten patients had developed their frontal sinuses. We observed no fluid in the frontal or sphenoid sinuses, neither before nor after surgery. At best, a mean of 23% of the maxillary sinuses were filled with fluid; thus, all sinuses had postoperatively areas of the mucosa that did not have contact with the fluid. A mean of 76% of the initial volume was present after 30 min in the maxillary sinuses. CONCLUSION: Fluid-depositing using nasal irrigation will not sufficiently or not at all get in contact with all the sinus mucosa despite of sinus surgery. Thus, the efficacy of topical deposition of antibiotics is presumably reduced.

Hyperbaric oxygen therapy augments tobramycin efficacy in experimental Staphylococcus aureus endocarditis.

Staphylococcus aureus infective endocarditis (IE) is a serious disease with an in-hospital mortality of up to 40%. Improvements in the effects of antibiotics and host responses could potentially benefit outcomes. Hyperbaric oxygen therapy (HBOT) represents an adjunctive therapeutic option. In this study, the efficacy of HBOT in combination with tobramycin in S. aureus IE was evaluated. A rat model of S. aureus IE mimicking the bacterial load in humans was used. Infected rats treated subcutaneously with tobramycin were randomised into two groups: (i) HBOT twice daily (n = 13); or (ii) normobaric air breathing (non-HBOT) (n = 17). Quantitative bacteriology, cytokine expression, valve vegetation size and clinical status were assessed 4 days post-infection. Adjunctive HBOT reduced the bacterial load in the aortic valves, myocardium and spleen compared with the non-HBOT group (P = 0.004, <0.001 and 0.01, respectively) and improved the clinical score (P <0.0001). Photoplanimetric analysis and weight of valve vegetations showed significantly reduced vegetations in the HBOT group (P <0.001). Key pro-inflammatory cytokines [IL-1ß, IL-6, keratinocyte-derived chemokine (KC) and vascular endothelial growth factor (VEGF)] were significantly reduced in valves from the HBOT group compared with the non-HBOT group. In conclusion, HBOT augmented tobramycin efficacy as assessed by several parameters. These findings suggest the potential use of adjunctive therapy in severe S. aureus IE.

Experimental Pseudomonas aeruginosa mediated rhino sinusitis in mink.

OBJECTIVES: The nasal and sinus cavities in children may serve as reservoirs for microorganisms that cause recurrent and chronic lung infections. This study evaluates whether the mink can be used as an animal model for studying Pseudomonas aeruginosa mediated rhino-sinusitis since there is no suitable traditional animal model for this disease. METHODS: Nasal tissue samples from infected and control mink were fixed in formalin, demineralized, and embedded in paraffin. A histological examination of sections from the infected animals revealed disintegration of the respiratory epithelium lining the nasal turbinates and swelling and edema of the submucosa. The expression of mucins and sialylated glycans was examined using immunohistochemistry. RESULTS: MUC1, MUC2 and MUC5AC were upregulated in the inoculated animals as a much stronger staining was present in the respiratory epithelium in the infected animals compared to the controls. The goblet cells in the nasal epithelium from the infected mink showed high affinity to the Maackia amurensis lectin and anti-asialo GM1 indicating a high concentration of α2-3 sialic acid respectively ßGalNAc1-4Galß containing glycans in these mucin producing cells. The nasal cavity in the infected mink shows features of carbohydrate expression comparable to what has been described in the respiratory system after Pseudomonas aeruginosa infection in humans. CONCLUSION: It is suggested that the mink is suitable for studying Pseudomonas aeruginosa mediated rhino-sinusitis.

Individual pharmacokinetic variation leads to underdosing of ciprofloxacin in some cystic fibrosis patients.

BACKGROUND: Ciprofloxacin (CIP) is frequently used when treating cystic fibrose (CF) patients with intermittent Pseudomonas aeruginosa (P. aeruginosa) lung colonization. However, approximately 20% of the patients progress to chronic infection despite early intervention. The aim of this study, was to investigate the pharmacokinetics of CIP, to evaluate if CYP3A4-related metabolism is involved and to find the optimal dose needed to eradicate intermittently colonizing bacteria in the lungs of CF patients. Methods An open-label, prospective pharmacokinetic study was performed. Twenty-two adult CF-patients were each given 500 mg CIP orally. One blood sample was taken at t = 0, and the following 12 hr, nine blood samples were collected. The optimal dose and interval was then calculated by Monte Carlo simulation. CYP3A4-activity was mesured using the Erythromycin Breath Test (ERMBT). Results A 14-fold variation in AUC for the 500 mg CIP (median 473.5 µg/ml × min), and a 30-fold variation in Cmax for CIP (median 2 µg/ml) was found. For CYP3A4-activity the variation was 8-fold. No correlation was found between the CYP3A4-activity and CIP-concentrations. The probability of eradicating intermittent P. aeruginosa colonization in the lungs of CF patients was found to be 57% (3 doses/day), when 500 mg CIP was given. It was calculated to be 89% (2 doses/day) and 94% (3 doses/day), respectivly if 750 mg CIP had been given. Conclusion A large pharmacokinetic difference of CIP in CF patiens was found, not explained by CYP3A4 variation. CIP should be given at 750 mg two or three times daily to adult CF patients with intermittently colonization. Pediatr Pulmonol. 2017;52:319-323. © 2016 Wiley Periodicals, Inc.

Sinus surgery postpones chronic Gram-negative lung infection: cohort study of 106 patients with cystic fibrosis.

BACKGROUND: In patients with cystic fibrosis (CF) the sinuses are a bacterial reservoir for Gram-negative bacteria (GNB). From the sinuses the GNB can repeatedly migrate to the lungs. In a one-year follow-up study, endoscopic sinus surgery (ESS) with adjuvant therapy reduced the frequency of pulmonary samples positive for GNB. We investigated whether the effect is sustained. METHODOLOGY: We report the effect of ESS and adjuvant therapy three years postoperatively in a CF cohort participating in this prospective clinical follow-up study. The primary endpoint was the lung infection status defined by Leeds criteria. RESULTS: One hundred and six CF patients underwent ESS; 27 had improved lung infection status after three years. The prevalence of patients free of lung colonization with GNB significantly increased from 16/106 patients (15%) preoperatively to 35/106 patients (33%) after three years. The total cohort had decreasing lung function during follow-up; however, in 27 patients with improved lung infection status lung function was stable. Revision surgery was performed in 31 patients (28%). CONCLUSION: ESS with adjuvant therapy significantly improves the lung infection status for at least three years in our cohort of patients with CF and may postpone chronic lung infection with GNB and thus stabilize lung function.

The phagocytic fitness of leucopatches may impact the healing of chronic wounds.

Chronic non-healing wounds are significantly bothersome to patients and can result in severe complications. In addition, they are increasing in numbers, and a challenging problem to the health-care system. Handling of chronic, non-healing wounds can be discouraging due to lack of improvement, and a recent explanation can be the involvement of biofilm infections in the pathogenesis of non-healing wounds. Therefore, new treatment alternatives to improve outcome are continuously sought-after. Autologous leucopatches are such a new, adjunctive treatment option, showing promising clinical effects. However, the beneficial effect of the patches are not understood fully, although a major contribution is believed to be from the release of stimulating growth factors from activated thrombocytes within the leucopatch. Because the leucopatches also contain substantial numbers of leucocytes, the aim of the present study was to investigate the activity of the polymorphonuclear neutrophils (PMNs) within the leucopatch. By means of burst assay, phagocytosis assay, migration assay, biofilm killing assay and fluorescence in-situ hybridization (FISH) assay we showed significant respiratory burst in PMNs, active phagocytosis and killing of Pseudomonas aeruginosa by the leucopatch. In addition, bacterial-induced migration of PMNs from the leucopatch was shown, as well as uptake of P. aeruginosa by PMNs within the leucopatch. The present study substantiated that at least part of the beneficial clinical effect in chronic wounds by leucopatches is attributed to the activity of the PMNs in the leucopatch.

New technology markedly improves hand-hygiene performance among healthcare workers after restroom visits.

The risks to patients from pathogens present on healthcare workers' (HCWs') hands are high; however, compliance with hand hygiene among HCWs is low. We devised a prospective intervention trial of a new hand-hygiene dispensing technology to improve HCWs' compliance with hand hygiene. Baseline hand-hygiene compliance was observed for three months before and after an intervention consisting of implementation of an electronic device that reminds people to comply with hand hygiene after restroom visits. Compliance in hand-hygiene performance after restroom visits increased among HCWs from 66% to 91% after the intervention.

Anti-Pseudomonas aeruginosa IgY antibodies augment bacterial clearance in a murine pneumonia model.

BACKGROUND: Oral prophylactic therapy by gargling with pathogen-specific egg yolk immunoglobulins (IgY) may reduce the initial airway colonization with Pseudomonas aeruginosa in cystic fibrosis (CF) patients. IgY antibodies impart passive immunization and we investigated the effects of anti-P. aeruginosa IgY antibodies on bacterial eradication in a murine pneumonia model. METHODS: P. aeruginosa pneumonia was established in Balb/c mice and the effects of prophylactic IgY administration on lung bacteriology, clinical parameters and subsequent inflammation were compared to controls. RESULTS: Prophylactic administration of IgY antibodies targeting P. aeruginosa significantly reduced the bacterial burden by 2-log 24h post-infection compared to controls and was accompanied by significantly reduced clinical symptom scores and successive inflammatory cytokine profile indicative of diminished lung inflammation. CONCLUSIONS: Passive immunization by anti-P. aeruginosa IgY therapy facilitates promptly bacterial clearance and moderates inflammation in P. aeruginosa lung infection and may serve as an adjunct to antibiotics in reducing early colonization.

Low efficacy of tobramycin in experimental Staphylococcus aureus endocarditis.

The empiric treatment of infective endocarditis (IE) varies widely and, in some places, a regimen of penicillin in combination with an aminoglycoside is administered. The increasing incidence of Staphylococcus aureus IE, poor tissue penetration by aminoglycosides and low frequency of penicillin-susceptible S. aureus may potentially lead to functional tobramycin monotherapy. Therefore, this study aimed to evaluate tobramycin monotherapy in an experimental S. aureus IE rat model. Catheter-induced IE at the aortic valves were established with S. aureus (NCTC 8325-4) and rats were randomised into untreated (n = 22) or tobramycin-treated (n = 13) groups. The treatment group received tobramycin once-daily. Animals were evaluated at 1 day post infection (DPI), 2 DPI or 3 DPI. Quantitative bacteriology and cytokine expression were measured for valves, myocardium and serum. A decrease of bacterial load was observed in valves and the spleens of the treated (n = 6) compared to the untreated group at 2 DPI (n = 8) (p ≤ 0.02 and p ≤ 0.01, respectively), but not at 3 DPI (n = 7). Quantitative bacteriology in the myocardium was not different between the groups. Keratinocyte-derived chemokine (KC) in the aortic valves was significantly reduced at 2 DPI in the tobramycin-treated group (p ≤ 0.03). However, the expression of interleukin (IL)-1b, IL-6 and granulocyte-colony stimulating factor (G-CSF) in the valves was not different between the two groups. In the myocardium, a significant reduction in IL-1b was observed at 2 DPI (p ≤ 0.001) but not at 3 DPI. Tobramycin as functional monotherapy only reduced bacterial load and inflammation transiently, and was insufficient in most cases of S. aureus IE.

A longitudinal study of lung bacterial pathogens in patients with primary ciliary dyskinesia.

In patients with primary ciliary dyskinesia (PCD), impaired mucociliary clearance leads to an accumulation of secretions in the airways and susceptibility to repeated bacterial infections. The primary aim of this study was to investigate the bacterial flora in non-chronic and chronic infections in the lower airways of patients with PCD. We retrospectively reviewed the presence of bacteria from patients with PCD during an 11-year period and genotyped 35 Pseudomonas aeruginosa isolates from 12 patients with chronic infection using pulsed-field gel electrophoresis. We identified 5450 evaluable cultures from 107 patients with PCD (median age 17 years, range 0-74 years) (median age at diagnosis 7.8 years, range 0-63 years). Haemophilus influenzae was the most frequent microorganism. Other common pathogens were P. aeruginosa, Streptococcus pneumoniae, Moraxella catarrhalis and Staphylococcus aureus. The number of patients colonized with P. aeruginosa at least once varied from 11 to 44 patients (15-47%) annually, and 42 patients (39%) met the criteria for chronic infection at least once. Pseudomonas aeruginosa was more frequently isolated in teenagers and adults than children (p 0.02) and the prevalence was significantly lower in patients with preschool (<6 years) PCD diagnosis (p 0.04). Ten out of 12 patients (83%) were chronically infected with a unique clone-type of P. aeruginosa. No sharing of clone-types or patient-to-patient transmission was observed. In conclusion, PCD patients were infected by a unique set of bacteria acquired in an age-dependent sequence. Pseudomonas aeruginosa frequently colonizes the lower respiratory tract and the incidence of chronic infection was higher than previously reported.

Anti-Pseudomonas aeruginosa IgY Antibodies Induce Specific Bacterial Aggregation and Internalization in Human Polymorphonuclear Neutrophils.

Polymorphonuclear neutrophils (PMNs) are essential cellular constituents in the innate host response, and their recruitment to the lungs and subsequent ubiquitous phagocytosis controls primary respiratory infection. Cystic fibrosis pulmonary disease is characterized by progressive pulmonary decline governed by a persistent, exaggerated inflammatory response dominated by PMNs. The principal contributor is chronic Pseudomonas aeruginosa biofilm infection, which attracts and activates PMNs and thereby is responsible for the continuing inflammation. Strategies to prevent initial airway colonization with P. aeruginosa by augmenting the phagocytic competence of PMNs may postpone the deteriorating chronic biofilm infection. Anti-P. aeruginosa IgY antibodies significantly increase the PMN-mediated respiratory burst and subsequent bacterial killing of P. aeruginosa in vitro. The mode of action is attributed to IgY-facilitated formation of immobilized bacteria in aggregates, as visualized by fluorescence microscopy and the induction of increased bacterial hydrophobicity. Thus, the present study demonstrates that avian egg yolk immunoglobulins (IgY) targeting P. aeruginosa modify bacterial fitness, which enhances bacterial killing by PMN-mediated phagocytosis and thereby may facilitate a rapid bacterial clearance in airways of people with cystic fibrosis.

ESCMID guideline for the diagnosis and treatment of biofilm infections 2014.

Biofilms cause chronic infections in tissues or by developing on the surfaces of medical devices. Biofilm infections persist despite both antibiotic therapy and the innate and adaptive defence mechanisms of the patient. Biofilm infections are characterized by persisting and progressive pathology due primarily to the inflammatory response surrounding the biofilm. For this reason, many biofilm infections may be difficult to diagnose and treat efficiently. It is the purpose of the guideline to bring the current knowledge of biofilm diagnosis and therapy to the attention of clinical microbiologists and infectious disease specialists. Selected hallmark biofilm infections in tissues (e.g. cystic fibrosis with chronic lung infection, patients with chronic wound infections) or associated with devices (e.g. orthopaedic alloplastic devices, endotracheal tubes, intravenous catheters, indwelling urinary catheters, tissue fillers) are the main focus of the guideline, but experience gained from the biofilm infections included in the guideline may inspire similar work in other biofilm infections. The clinical and laboratory parameters for diagnosing biofilm infections are outlined based on the patient's history, signs and symptoms, microscopic findings, culture-based or culture-independent diagnostic techniques and specific immune responses to identify microorganisms known to cause biofilm infections. First, recommendations are given for the collection of appropriate clinical samples, for reliable methods to specifically detect biofilms, for the evaluation of antibody responses to biofilms, for antibiotic susceptibility testing and for improvement of laboratory reports of biofilm findings in the clinical microbiology laboratory. Second, recommendations are given for the prevention and treatment of biofilm infections and for monitoring treatment effectiveness. Finally, suggestions for future research are given to improve diagnosis and treatment of biofilm infections.

Rapid identification of Stenotrophomonas maltophilia by peptide nucleic acid fluorescence in situ hybridization.

The objective of this study was to develop a novel peptide nucleic acid (PNA) probe for Stenotrophomonas maltophilia identification by fluorescence in situ hybridization (FISH). The probe was evaluated using 33 human and veterinary clinical S. maltophilia isolates and 45 reference strains representing common bacterial species in the respiratory tract. The probe displayed 100% sensitivity and 100% specificity on pure cultures and allowed detection in sputum from cystic fibrosis patients. The detection limit was 10(4) CFU/mL in spiked tracheal aspirate and bronchoalveolar lavage from healthy horses. Altogether the study shows that this species-specific PNA FISH probe facilitates rapid detection of S. maltophilia in biological specimens.

Nitric oxide production by polymorphonuclear leucocytes in infected cystic fibrosis sputum consumes oxygen.

Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients is characterized by persisting mucoid biofilms in hypoxic endobronchial mucus. These biofilms are surrounded by numerous polymorphonuclear leucocytes (PMNs), which consume a major part of present molecular oxygen (O(2)) due to production of superoxide (O(2)(-)). In this study, we show that the PMNs also consume O(2) for production of nitric oxide (NO) by the nitric oxide synthases (NOS) in the infected endobronchial mucus. Fresh expectorated sputum samples (n = 28) from chronically infected CF patients (n = 22) were analysed by quantifying and visualizing the NO production. NO production was detected by optode measurements combined with fluorescence microscopy, flow cytometry and spectrophotometry. Inhibition of nitric oxide synthases (NOS) with N(G) -monomethyl-L-arginine (L-NMMA) resulted in reduced O(2) consumption (P < 0·0008, n = 8) and a lower fraction of cells with fluorescence from the NO-indicator 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM) (P < 0·002, n = 8). PMNs stained with DAF-FM and the superoxide indicator hydroethidine (HE) and host cells with inducible NOS (iNOS) were identified in the sputum. In addition, the production of the stable end-products of NO in CF sputum was correlated with the concentration of PMNs; NO(3)(-) (P < 0·04, r = 0·66, n = 10) and NO(2)(-) (P< 0·006, r = 0·78, n = 11). The present study suggests that besides consumption of O(2) for production of reactive oxygen species, the PMNs in CF sputum also consume O(2) for production of NO.

Pharmacokinetic variability of clarithromycin and differences in CYP3A4 activity in patients with cystic fibrosis.

BACKGROUND: To investigate the correlation between CYP3A4/5 activity and clarithromycin metabolism, and between CYP3A activity and CYP3A genotype. METHODS: This is an open-label, prospective pharmacokinetic study evaluating CYP3A activity using The Erythromycin Breath Test. Eight blood samples were collected within 12h after clarithromycin 500 mg was administered orally. The clarithromycin concentrations were measured by liquid chromatography-tandem mass spectrometry. AUC, Tmax and Cmax were calculated. Selected Single Nucleotide polymorphisms in CYP3A4/5 genes were assessed by PCR and single base extension. RESULTS: Twenty-one chronically infected patients were included. An 8-fold variation in the CYP3A4 activity, 10-fold variation in AUC for clarithromycin (median 881 µg/mL × min), and a 16-fold variation in Cmax for clarithromycin (median 3.4 µg/mL) were found. A linear correlation between the CYP3A4-activity and clarithromycin metabolism was demonstrated (P < 0.05). CONCLUSION: The large variation in the clarithromycin pharmacokinetics in cystic fibrosis patients may cause treatment failure. The Erythromycin Breath Test could be valuable in identifying cystic fibrosis patients in risk of treatment failure/drug toxicity.

Clinical effects of sinus surgery and adjuvant therapy in cystic fibrosis patients - can chronic lung infections be postponed?

BACKGROUND: The paranasal sinuses can be a bacterial reservoir for pulmonary infections in patients with cystic fibrosis (CF) METHODOLOGY: In this prospective, non-randomised, uncontrolled, intervention cohort study, the clinical effect of sinus surgery followed by two weeks` intravenous antibiotics, 6 months` antibiotic nasal irrigations was assessed in 106 CF patients. RESULTS: One year after sinus surgery, the prevalence of intermittently colonised patients had decreased by 38%, while the prevalence of non-colonised patients had increased by 150%. The frequency of pulmonary samples with CF pathogens was reduced after surgery. Specific IgG against P. aeruginosa decreased after six months. Additionally, the self reported symptoms of chronic rhinosinusitis and quality of life improved. CONCLUSION: Combined sinus surgery and postoperative systemic and topical antibiotic treatment significantly reduced the frequency of pulmonary samples positive for CF pathogens in the first year after sinus surgery.

Early treatment with inhaled antibiotics postpones next occurrence of Achromobacter in cystic fibrosis.

OBJECTIVES: In this nationwide retrospective study, we analysed species distribution, antimicrobial susceptibility and time to next occurrence of Achromobacter in Danish cystic fibrosis (CF) patients from 2000 to 2011. METHODS: Thirty-four primary isolates were identified to species level and subjected to antimicrobial susceptibility testing. Effectiveness of early antimicrobial treatment was assessed by a Kaplan-Meier estimation of time to recurrence. RESULTS: Achromobacter xylosoxidans accounted for 13 (38%) of the isolates, and an unnamed species accounted for 11 (32%) of the isolates. Meropenem, piperacillin-tazobactam and trimethoprim-sulfamethoxazole were highly active against chemotherapy-naïve Achromobacter, while ceftazidime, colistin and tobramycin were judged adequate for inhalation therapy. Fifty-five percent of 25 patients treated with inhaled ceftazidime, colistin, or tobramycin remained free of Achromobacter three years after acquisition, in contrast to 17% of 22 patients who did not receive inhaled antibiotics (P<0.01). CONCLUSIONS: Early treatment with inhaled antibiotics may prevent or postpone chronic infection with Achromobacter in CF patients.

Typing of Pseudomonas aeruginosa from hemorrhagic pneumonia in mink (Neovison vison).

Hemorrhagic pneumonia in mink (Neovison vison) is caused by Pseudomonas aeruginosa and is an acute and fatal disease in farmed mink. Earlier work has demonstrated that some outbreaks of hemorrhagic pneumonia are caused by pathogenic strains while most outbreaks are caused by local strains. The objective of this study was to determine the genetic and geographical relationship among outbreaks of hemorrhagic pneumonia by pulsed-field gel electrophoresis typing of P. aeruginosa isolates. Furthermore, chosen isolates were typed by a commercial genotyping method based on single nucleotide polymorphisms (SNPs) and compared to a larger dataset of human and environmental origin. The bacterial isolates were obtained from diagnostic samples from 2002 to 2009 and contained 164 isolates from 95 outbreaks on 90 farms. Our results show that most outbreaks of hemorrhagic pneumonia in mink are caused by distinct strains of P. aeruginosa. We also identified related P. aeruginosa strains which, together with two prevalent but unrelated clones, caused one third of the outbreaks of hemorrhagic pneumonia supporting the sparse literature on this subject. None of the SNP typed strains were identified in a large dataset of human and environmental origin.