Infection In CF Research Articles

A multinational report on SARS-CoV-2 infection outcomes in people with CF and Aspergillus infection or ABPA

BackgroundAspergillus infection is known to be associated with worse respiratory outcomes in people with CF (pwCF) and is a well-recognised complication of severe SARS-CoV-2 infection. The aim of this observational cross-sectional study was to examine the association of pre-existing Aspergillus infection and/or allergic bronchopulmonary aspergillosis (ABPA) in pwCF and severity of COVID-19. MethodsData on SARS-CoV-2 infections in pwCF from January 2020 to June 2021 were collected by the European Cystic Fibrosis Society Patient Registry. The primary outcome was COVID-19 severity measured by hospitalisation comparing those with Aspergillus infection and/or ABPA in the 12 months preceding COVID-19 and those without. ResultsIn total, 1095 pwCF were diagnosed with SARS-CoV-2 and information on pre-existing Aspergillus/ABPA status was available from 807. PwCF and SARS-CoV-2 in the Aspergillus/ABPA group (n = 153), in comparison to the non-Aspergillus/ABPA group (n = 654), were more likely to be hospitalised (adjusted OR 1.79 (1.19 to 2.85); p = 0.005) and their disease course was more likely to be complicated by sepsis (adjusted OR 7.78 (1.78 to 49.43); p = 0.008). The association with hospital admission was no longer significant after excluding patients with ABPA. Secondary analysis comparing pwCF who received antifungal treatment (n = 18), versus those who did not (n = 474) during COVID-19, showed a higher rate of hospitalisation (p < 0.001); intensive care unit admission (p < 0.001), and requirement for invasive ventilation (p < 0.001) in the antifungal treated group. ConclusionWe show that pre-existing Aspergillus/ABPA is associated with increased rates of hospitalisation and sepsis during COVID-19 in pwCF.

Limited effects of azithromycin on the oropharyngeal microbiome in children with CF and early pseudomonas infection

BackgroundTobramycin inhalation solution (TIS) and chronic azithromycin (AZ) have known clinical benefits for children with CF, likely due to antimicrobial and anti-inflammatory activity. The effects of chronic AZ in combination with TIS on the airway microbiome have not been extensively investigated. Oropharyngeal swab samples were collected in the OPTIMIZE multicenter, randomized, placebo-controlled trial examining the addition of AZ to TIS in 198 children with CF and early P. aeruginosa infection. Bacterial small subunit rRNA gene community profiles were determined. The effects of TIS and AZ were assessed on oropharyngeal microbial diversity and composition to uncover whether effects on the bacterial community may be a mechanism of action related to the observed changes in clinical outcomes.ResultsSubstantial changes in bacterial communities (total bacterial load, diversity and relative abundance of specific taxa) were observed by week 3 of TIS treatment for both the AZ and placebo groups. On average, these shifts were due to changes in non-traditional CF taxa that were not sustained at the later study visits (weeks 13 and 26). Bacterial community measures did not differ between the AZ and placebo groups.ConclusionsThis study provides further evidence that the mechanism for AZ’s effect on clinical outcomes is not due solely to action on airway microbial composition.

ALPINE2: Efficacy and safety of 14-day vs 28-day inhaled aztreonam for Pa eradication in children with cystic fibrosis

BackgroundAntibiotic eradication therapies recommended for newly isolated Pseudomonas aeruginosa (Pa) in people with cystic fibrosis (pwCF) can be burdensome. ALPINE2 compared the efficacy and safety of a shortened 14-day course of aztreonam for inhalation solution (AZLI) with 28-day AZLI in paediatric pwCF. MethodsALPINE2 (a double-blind, phase 3b study) included children aged 3 months to <18 years with CF and new-onset Pa infection. Participants were randomized to receive 75 mg AZLI three times daily for either 28 or 14 days followed by 14 days' matched placebo. The primary endpoint was rate of primary Pa eradication (no Pa detected during the 4 weeks post AZLI treatment). Non-inferiority was achieved if the lower 95% CI bound of the treatment difference between the two arms was above −20%. Secondary endpoints included assessments of Pa recurrence during 108 weeks of follow-up after primary eradication. Safety endpoints included treatment-emergent adverse events (TEAEs). ResultsIn total, 149 participants were randomized (14-day AZLI, n = 74; 28-day AZLI, n = 75) and 142 (95.3%) completed treatment. Median age: 6.0 years (range: 0.3–17.0). Baseline characteristics were similar between treatment arms. Primary Pa eradication rates: 14-day AZLI, 55.9%; 28-day AZLI, 63.4%; treatment difference (CI), −8.0% (−24.6, 8.6%). Pa recurrence rates at follow-up end: 14-day AZLI, 54.1% (n = 20/37); 28-day AZLI, 41.9% (n = 18/43). TEAEs were similar between treatment arms. No new safety signals were observed. ConclusionsNon-inferiority of 14-day AZLI versus 28-day AZLI was not demonstrated. Both courses were well tolerated, further supporting AZLI short-term safety in paediatric and adolescent pwCF. ClinicalTrials.govNCT03219164

P260 Co-culture of Prevotella spp. and Pseudomonas aeruginosa from chronic cystic fibrosis infection in artificial sputum medium

Previous research using agar well diffusion assays revealed that Pseudomonas aeruginosa (PA) isolates from chronic CF infection, grown aerobically and anaerobically, inhibited the growth of other clinically relevant species. This study aimed to determine if this observed inhibition was also exhibited in conditions more physiologically representative of the CF airways.

Overexpression of auxin/indole-3-acetic acid gene MdIAA24 enhances Glomerella leaf spot resistance in apple (Malus domestica)

Auxin is throughout the entire life process of plants and is involved in the crosstalk with other hormones, yet its role in apple disease resistance remains unclear. In this study, we investigated the function of auxin/indole-3-acetic acid (IAA) gene MdIAA24 overexpression in enhancing apple resistance to Glomerella leaf spot (GLS) caused by Colletotrichum fructicola (Cf). Analysis revealed that, upon Cf infection, 35S::MdIAA24 plants exhibited enhanced superoxide dismutase (SOD) and peroxidase (POD) activity, as well as a greater amount of glutathione (reduced form) and ascorbic acid accumulation, resulting in less H2O2 and superoxide anion (O2.−) in apple leaves. Furthermore, 35S::MdIAA24 plants produced more protocatechuic acid, proanthocyanidins B1, proanthocyanidins B2 and chlorogenic acid when infected with Cf. Following Cf infection, 35S::MdIAA24 plants presented lower levels of IAA and jasmonic acid (JA), but higher levels of salicylic acid (SA), along with the expression of related genes. The overexpression of MdIAA24 was observed to enhance the activity of chitinase and β-1,3-glucanase in Cf-infected leaves. The results indicated the ability of MdIAA24 to regulate the crosstalk between IAA, JA and SA, and to improve reactive oxygen species (ROS) scavenging and defense-related enzymes activity. This jointly contributed to GLS resistance in apple.

S10.5a Fungal respiratory infections in cystic fibrosis patients in the Middle East

S10.5 Fungal respiratory infections in Cystic Fibrosis, September 24, 2022, 10:30 AM - 12:00 PMCystic Fibrosis (CF) is among the most common genetic disorders, which involves multiple organs including the respiratory tract. CF is thought to be an uncommon disease in the Middle East (ME). However, the prevalence is estimated at 1 in 30 000-50 000, while the incidence is estimated at 1 in 2000-5800 live births. Several studies from ME revealed that many children with CF in these populations probably remain undiagnosed due to lack of clinical suspicion and proper diagnostic facilities. According to the experts’ idea, CF may be more common in Iran than expected before. Chronic colonization of the airways of CF patients and infections due to a wide variety of opportunistic fungal pathogens including Aspergillus, Candida, Scedosporium species, Exophiala dermatitidis, Rasamsonia argillacea complex, and Lomentospora prolificans are currently increasing. On the other hand, the resistance of these opportunistic pathogens to commonly available antifungals challenges therapeutic options and consequently endanger the CF patients’ life. Dissimilar to bacterial colonization or infections, the epidemiology and pathogenicity of colonization and fungal respiratory infections in CF are less known. According to our recent study, the prevalence rate of respiratory colonization was reported as 73.3%. Among mold isolates, Aspergillus was also the most common genus followed by Scedosporium species. In contrast to the reports from western countries, A. flavus was also identified as the most prevalent species of Aspergillus from ME countries including Iran and India. In some studies, allergic bronchopulmonary aspergillosis (ABPA) in CF patients from ME was evaluated. In our recent experience from Iran, of 86 patients with CF, 9 (10.5%) cases were met ABPA diagnosis. A. flavus was the most common agent followed by A. fumigatus, A. terreus and A. tubingensis. A significant resistance of Scedosporium and Aspergillus isolates from CF patients against the main antifungal agents in invasive fungal infections therapy was reported in different studies. According to these realities, there are a few reports on the Research Topic ‘Fungal Respiratory Infections and Colonization in CF’ from Iran and some other ME countries. Therefore, in this presentation, we are going to highlight our experiences and other published data from Iran and ME in this field including clinical presentations, fungal species involved, diagnosis strategies, and in vitro antifungal susceptibility patterns of fungal isolates from CF patients, and common treatments and prophylactic strategies.

Maintenance tobramycin primarily affects untargeted bacteria in the CF sputum microbiome

RationaleThe most common antibiotic used to treat people with cystic fibrosis (PWCF) is inhaled tobramycin, administered as maintenance therapy for chronic Pseudomonas aeruginosa lung infections. While the effects of inhaled...

CFTR Modulator Therapy Enhances Peripheral Blood Monocyte Contributions to Immune Responses in People With Cystic Fibrosis.

BackgroundCFTR modulators decrease some etiologies of CF airway inflammation; however, data indicate that non-resolving airway infection and inflammation persist in individuals with CF and chronic bacterial infections. Thus, identification of therapies that diminish airway inflammation without allowing unrestrained bacterial growth remains a critical research goal. Novel strategies for combatting deleterious airway inflammation in the CFTR modulator era require better understanding of cellular contributions to chronic CF airway disease, and how inflammatory cells change after initiation of CFTR modulator therapy. Peripheral blood monocytes, which traffic to the CF airway, can develop both pro-inflammatory and inflammation-resolving phenotypes, represent intriguing cellular targets for focused therapies. This therapeutic approach, however, requires a more detailed knowledge of CF monocyte cellular programming and phenotypes.Material and MethodsIn order to characterize the inflammatory phenotype of CF monocytes, and how these cells change after initiation of CFTR modulator therapy, we studied adults (n=10) with CF, chronic airway infections, and the CFTR-R117H mutations before and 7 days after initiation of ivacaftor. Transcriptomes of freshly isolated blood monocytes were interrogated by RNA-sequencing (RNA-seq) followed by pathway-based analyses. Plasma concentrations of cytokines and chemokines were evaluated by multiplex ELISA.ResultsRNAseq identified approximately 50 monocyte genes for which basal expression was significantly changed in all 10 subjects after 7 days of ivacaftor. Of these, the majority were increased in expression post ivacaftor, including many genes traditionally associated with enhanced inflammation and immune responses. Pathway analyses confirmed that transcriptional programs were overwhelmingly up-regulated in monocytes after 7 days of ivacaftor, including biological modules associated with immunity, cell cycle, oxidative phosphorylation, and the unfolded protein response. Ivacaftor increased plasma concentrations of CXCL2, a neutrophil chemokine secreted by monocytes and macrophages, and CCL2, a monocyte chemokine.ConclusionsOur results demonstrate that ivacaftor causes acute changes in blood monocyte transcriptional profiles and plasma chemokines, and suggest that increased monocyte inflammatory signals and changes in myeloid cell trafficking may contribute to changes in airway inflammation in people taking CFTR modulators. To our knowledge, this is the first report investigating the transcriptomic response of circulating blood monocytes in CF subjects treated with a CFTR modulator.

Varietal Breakdown to Red Rot in Sugarcane Revealed by Comparing Two Colletotrichum falcatum Inoculation Methods

Colletotrichum falcatum Went causing red rot is a major constraint to cane production and productivity across sugarcane growing countries in Asia. The fungal pathogen exhibits enormous variation under field conditions; the pathogenic variants emerge regularly in tune with deployment of new host varieties for cultivation making the resistant to susceptible referred as ‘varietal breakdown’. Although such phenomena occurred regularly, how the varieties succumb to the C. falcatum pathotypes is not clearly established, and hence, longevity of red rot-resistant varieties become unpredictable under field conditions. The soil-borne inoculum surviving as crop debris is the known source of C. falcatum (Cf) inoculum to cause infection in the field, probably after repeated attempts in a variety which was hitherto resistant. Hence, a detailed study was conducted with a set of Cf pathotypes varying in their virulence and ten varieties with their disease reactions vary from moderately resistant (MR) to highly susceptible (HS) by inoculating the pathogen by the plug method on standing canes and applying Cf inoculum to the soil, under field conditions. The three seasons study clearly indicated that disease reactions in sugarcane varieties to different Cf pathotypes in the plug method did not vary among the seasons, whereas the sugarcane varieties behaved differently for disease development from soil-borne inoculum. When disease development from the two inoculation methods was compared with respect to their known disease reaction, MR and HS varieties showed a similar pattern. However, four of the five moderately susceptible (MS) varieties showed a deviation for higher disease development from soil inoculum to certain pathotypes. Such disease development in the trial from soil inoculum is reflected by a similar behaviour in disease endemic locations, where they succumbed to the pathogen. Overall, the study explains susceptibility of sugarcane varieties for Cf infection from the inoculum surviving in the soil in due course in the field, although their host reactions are MR or MS. Also these findings provide an evidence for varietal breakdown to C. falcatum in sugarcane from soil-borne inoculum under field conditions, for the first time.

Microbiological evaluation of UV disinfection effectiveness in a specialist cystic fibrosis clinic

The aim of the study was to evaluate the impact of manual cleaning and manual cleaning followed by Ultraviolet-C disinfection on the colony forming units of bacteria retrievable from equipment and surfaces within clinic rooms following a CF outpatient encounter. While UV disinfection has proven to be effective within general healthcare settings, it has not been evaluated in a CF centre.Microbiological sampling was performed following outpatient encounters involving 11 adult patients with CF and chronic infection with P.aeruginosa, MRSA or E. coli ESBL.The results of this study suggest that manual cleaning followed by UV-C disinfection is more effective than manual cleaning alone at reducing environmental contamination within a CF clinic and that UV-C isinfection is likely to reduce the risk of fomite transmission in the CF outpatient setting.

Campylobacter fetus impairs barrier function in HT-29/B6 cells through focal tight junction alterations and leaks.

Infections by Campylobacter species are the most common foodborne zoonotic disease worldwide. Campylobacter jejuni and C. coli are isolated most frequently from human stool samples, but severe infections by C. fetus (Cf), which can cause gastroenteritis, septicemia, and abortion, are also found. This study aims at the characterization of pathological changes in Cf infection using an intestinal epithelial cell model. The Cf-induced epithelial barrier defects appeared earlier than those of avian Campylobacter species like C. jejuni/C. coli. Two-path impedance spectroscopy (2PI) distinguished transcellular and paracellular resistance contributions to the overall epithelial barrier impairment. Both transcellular and paracellular resistance of Cf-infected HT-29/B6 monolayers were reduced. The latter was attributed to activation of active anion secretion. Western blot analysis showed no decrease in tight junction (TJ) protein expression (claudin-1, -2, -3, and -4) but showed redistribution of claudin-1 off the TJ domain. In addition, Cf induced epithelial cell death, cell detachment, and lesions (focal leaks), as the result of which macromolecule flux (10-kDa dextran) was increased in Cf-invaded cell monolayers. In conclusion, barrier dysfunction from Cf infection was due to TJ protein redistribution, cell death induction, and leak formation, resulting in bacterial translocation, ion leak flux, and antigen uptake (leaky gut).

121 Multiple oxidative stress response genes undergo adaptive evolution during chronic CF infection by Burkholderia cenocepacia ST32

121 Multiple oxidative stress response genes undergo adaptive evolution during chronic CF infection by Burkholderia cenocepacia ST32

Within-Host Evolution of Burkholderia pseudomallei during Chronic Infection of Seven Australasian Cystic Fibrosis Patients.

ABSTRACTCystic fibrosis (CF) is a genetic disorder characterized by progressive lung function decline. CF patients are at an increased risk of respiratory infections, including those by the environmental bacterium Burkholderia pseudomallei, the causative agent of melioidosis. Here, we compared the genomes of B. pseudomallei isolates collected between ~4 and 55 months apart from seven chronically infected CF patients. Overall, the B. pseudomallei strains showed evolutionary patterns similar to those of other chronic infections, including emergence of antibiotic resistance, genome reduction, and deleterious mutations in genes involved in virulence, metabolism, environmental survival, and cell wall components. We documented the first reported B. pseudomallei hypermutators, which were likely caused by defective MutS. Further, our study identified both known and novel molecular mechanisms conferring resistance to three of the five clinically important antibiotics for melioidosis treatment. Our report highlights the exquisite adaptability of microorganisms to long-term persistence in their environment and the ongoing challenges of antibiotic treatment in eradicating pathogens in the CF lung. Convergent evolution with other CF pathogens hints at a degree of predictability in bacterial evolution in the CF lung and potential targeted eradication of chronic CF infections in the future.

High virulence sub-populations in Pseudomonas aeruginosa long-term cystic fibrosis airway infections

BackgroundPseudomonas aeruginosa typically displays loss of virulence-associated secretions over the course of chronic cystic fibrosis infections. This has led to the suggestion that virulence is a costly attribute in chronic infections. However, previous reports suggest that overproducing (OP) virulent pathotypes can coexist with non-producing mutants in the CF lung for many years. The consequences of such within-patient phenotypic diversity for the success of this pathogen are not fully understood. Here, we provide in-depth quantification of within-host variation in the production of three virulence associated secretions in the Liverpool cystic fibrosis epidemic strain of P. aeruginosa, and investgate the effect of this phenotypic variation on virulence in acute infections of an insect host model.ResultsWithin-patient variation was present for all three secretions (pyoverdine, pyocyanin and LasA protease). In two out of three patients sampled, OP isolates coexisted with under-producing mutants. In the third patient, all 39 isolates were under-producers of all three secretions relative to the transmissible ancestor LESB58. Finally, this phenotypic variation translated into variation in virulence in an insect host model.ConclusionsWithin population variation in the production of P. aeruginosa virulence-associated secretions can lead to high virulence sub-populations persisting in patients with chronic CF infections.

91 Genomic evolution of Burkholderia contaminans ST872 during chronic CF infection

91 Genomic evolution of Burkholderia contaminans ST872 during chronic CF infection

An international, multicentre evaluation and description of Burkholderia pseudomallei infection in cystic fibrosis.

BackgroundSeveral cases of Burkholderia pseudomallei infection in CF have been previously reported. We aimed to identify all cases globally, risk factors for acquisition, clinical consequences, and optimal treatment strategies.MethodsWe performed a literature search to identify all published cases of B. pseudomallei infection in CF. In addition we hand-searched respiratory journals, and contacted experts in infectious diseases and CF around the world. Supervising clinicians for identified cases were contacted and contemporaneous clinical data was requested.Results25 culture-confirmed cases were identified. The median age at acquisition was 21 years, mean FEV1 % predicted was 60 %, and mean BMI was 19.5 kg/m2. The location of acquisition was northern Australia or south-east Asia for most. 19 patients (76 %) developed chronic infection, which was usually associated with clinical decline. Successful eradication strategies included a minimum of two weeks of intravenous ceftazidime, followed by a consolidation phase with trimethoprim/sulfamethoxazole, and this resulted in a higher chance of success when instituted early. Three cases of lung transplantation have been recorded in the setting of chronic B. pseudomallei infection.ConclusionChronic carriage of B. pseudomallei in patients with CF appears common after infection, in contrast to the non-CF population. This is often associated with an accelerated clinical decline. Lung transplantation has been performed in select cases of chronic B. pseudomallei infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-015-0109-9) contains supplementary material, which is available to authorized users.

EPS06.4 Upper airway infection and inflammation in CF and healthy controls during exacerbation and stable phases

Objectives Upper airway (UAW) infections are common in CF patients with nasal congestion, impaired climate function and reduced quality of life. Moreover, by postnasal drip, infections can descend to the lungs. Actually, there are no data comparing UAW infection and inflammation in CF and healthy controls in stable phases and during exacerbation. Methods We collected epithelial lining fluid from 49 CF patients and 38 healthy controls by nasal lavage in stable phases and during UAW infection. Microbiological (only CF cohort), cytological and immunological analyses (NE/IL-6/IL-8/IL-1β/MMP-9/TIMP-1) were performed. Results During UAW infection all measured inflammatory mediators increased in both, CF patients and the control cohort. Whereas levels of IL-6 and IL-8 were significantly higher in CF under stable conditions compared to healthy controls, the levels of the control cohort exceeded those of CF patients during infection. Age-stratified analyses showed higher releases of mediators during acute UAW infection in CF patients ≤12 years, especially for MMP-9, IL-8 and TIMP-1. These findings were not present in controls. Conclusion In CF patients, chronic inflammation with higher values of inflammatory mediators compared to healthy controls was observed. However, the increase of inflammation during UAW infection is not higher in CF compared to healthy controls. In contrast, for all measured parameters except TIMP-1 a weaker increase was observed in CF, suggesting a deregulation of the immune system in CF with a decreased ability of mediator release. This hypothesis is also supported by the observation of higher releases of MMP-9, TIMP-1 and IL-8 in younger CF patients.

63 Pseudomonas aeruginosa pulmonary infection in CF patients in a Brazilian reference center: Antibody response monitoring

Objective The diagnosis of P. aeruginosa ( P.a .) pulmonary infection in CF is often difficult, due to the lack of a representative clinical specimen. In this study, we sought to evaluate the prognostic and diagnostic values of a serological test for detection of specific serum IgG antibodies to P.a. in a longitudinal analysis. Methods 78 patients were classified according to their P.a. colonization/infection status (Leeds criteria) and their antibody levels were evaluated in different periods of serum sample collection by an ELISA technique previously standardized with a polyvalent P. aeruginosa antigen (St-Ag:1–17). Results The antibody levels increased progressively over time and we could detect the presence of infection until 15 months before the first positive microbiological culture for P.a . Patients with positive antibody levels in the baseline showed a higher risk of evolution in the colonization/infection status ( P.a. negative to P.a . positive) (OR = 3.13, p P.a. in the baseline showed significantly higher antibody levels in 2 of 4 periods of sample collection. Conclusion The detection of specific serum IgG antibodies to P.a. may be an useful diagnostic tool for the early detection of P.a. pulmonary infection in CF, complementing microbiological results, which may allow the early intervention with antimicrobial therapy and decrease the decline of the pulmonary function.

88 Prevalence and characterization of unusual Staphylococcus aureus strains with a mucoid phenotype recovered from the airways of cystic fibrosis patients

Objectives Staphylococcus aureus is frequently isolated from the respiratory tract already in early childhood and often persists for extended periods. Mucoid bacterial colony morphology has been described for Pseudomonas aeruginosa, the most prominent pathogen in CF, but not for S. aureus. Recently, we identified mucoid isolates also for S. aureus. To determine the prevalence and the underlying mechanism of mucoid S. aureus isolates we used S. aureus isolates collected during two independent studies including 371 CF patients. Methods To determine the underlying mechanism of mucoidy, the ica promoter region of all isolates and the entire ica operon of selected strains were sequenced. Biofilm formation was determined by a microtiter plate assay. Mucoid and normal isolates of one patient were characterized in terms of capsule expression and phagocytosis by neutrophils. Results From the respiratory specimens of 8 patients (prevalence of 2.2%) mucoid S. aureus isolates were recovered. M ucoid isolates were strong biofilm producers. Mucoidy was associated with a 5-bp deletion in the ica promoter region. Subsequent non-mucoid isolates, which also carried a 5-bp deletion, harbored compensatory mutations . Transformation of 5-bp deletion carrying normal strains with a vector expressing intact ica restored mucoidy. In contrast to the normal phenotype, mucoid strains were protected against phagocytosis by neutrophils. Conclusion Although mucoid S. aureus strains are rarely identified during chronic airway infection in CF, biofilm hyper-production seems to be an effective strategy for protection against phagocytosis by neutrophils.

319 Nebulised temocillin for prophylaxis against Burkholderia vietnamiensis in an adult with cystic fibrosis

Objectives To illustrate the use of nebulised temocillin for prophylaxis in CF and chronic Burkholderia infection in a 29-year-old male. Methods Retrospective data collection from medical notes, included spirometry, CRP, frequency of IV antibiotics (14-day courses), and symptomatology. Data was collected for pre and post temocillin periods. Results Baseline spirometry: FEV1 66% pred., FVC 89% pred. Between ages 23 and 27 years, he had 2 courses of IV antibiotics yearly for exacerbations. FEV1 fell to a minimum of 55% pred., and CRP ( 100 on 3 occasions), and worsened spirometry (minimum FEV1 37% pred. and FVC 40% pred.). Worsening symptoms were recorded. Following onset of nebulised temocillin alternate months (7 months), frequency of IV antibiotics decreased to 4 courses (3 courses whilst off temocillin). Maximum CRP 42, and minimum FEV1 50% pred., significant symptom improvement was reported. Continuous nebulised temocillin was then started. No IV antibiotics were given in the following 4-month period. Conclusion Temocillin is a narrow spectrum penicillin stable to most β-lactamases and ESBLs. It demonstrates in vitro activity against B. cepacia . It does not induce β-lactamase production. Clinical data suggests benefit of IV temocillin for CF patients with B. cepacia . This case illustrates that temocillin may be a well tolerated and effective nebulised antibiotic for CF patients with Burkholderia .