Osteoradionecrosis of the mandible after radiotherapy for head and neck cancer: risk factors and dose-volume correlations.

Background: The project aimed at determining the incidence of mandibular osteoradionecrosis (ORN) after radiotherapy, possible risk factors, and mandibular dose-volume effects in a large cohort of head and neck cancer patients (HNC). Methods: The cohort consisted of 1224 HNC patients treated with 66-68 Gy in 2007-2015 predominantly with IMRT. ORN cases were defined from clinical observations at follow-up and through hospital code diagnostics after oral-maxillofacial surgery and cross-checked with the national Danish Head and Neck Cancer database. In a nested case-control study, patients with ORN cases were matched with two controls (1:2) and pre-RT dental procedures including surgery to the mandible were documented. Multivariable Cox regression analysis was applied using demographic and treatment variables including dental procedures, smoking and tumor characteristics, and combined with dosimetric data. Mean mandibular dose (Dmean) was pre-selected for the multivariable model. Results: ORN was recorded in 56 cases (4.6%) with a median time to event of 10.9 months (range 1.8-89.7) after RT, 90% occurred within 37.4 months. Median follow-up time was 22 months (0.3-95). Average Dmean was significantly higher in the ORN event cohort and significant dose-volume differences were observed for population mean DVH doses between 30 Gy and 60 Gy. In univariable analysis, smoking (HR = 1.69; CI 1.14-2.5), pre-RT surgery/tooth extraction (HR = 2.76; 1.48-5.14), and several dosimetric parameters including Dmean (HR = 1.05, 1.02-1.08) were all significantly associated with ORN. Dmean and surgery/tooth extraction remained significant predictors of ORN in multivariable analysis, HR = 1.04 (CI 1.01-1.07) and HR = 2.09 (CI 1.1-3.98), respectively, while smoking only retained its significance in an interaction analysis with pre-RT dental procedures. Conclusion: The onset of ORN of the mandible was early (median 10.8 months) and the incidence low (4.6%) after IMRT in HNC cancer patients. Surgery to the mandible and pre-RT tooth extraction, tobacco smoking, and treatment dose were associated with the development of ORN.

Relationship between patient and physician-rated xerostomia and dose distribution to the oral cavity and salivary glands for head and neck cancer patients after radiotherapy.

Introduction: Xerostomia is a frequent complication after curative intended radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC). Assessment of xerostomia is commonly done by the physician. The aim of this study is to investigate the relation between patient and physician-rated xerostomia and to predict the degree of xerostomia from patients with self-reported xerostomia based on delivered doses to the oral cavity, parotid, and submandibular glands. Material and methods: During a 2-year period, consecutive HNSCC patients attending the follow-up clinic were included. All included patients had self-reported xerostomia, and completed the disease-specific EORTC QLQ-H&N35 questionnaire. The physician assessed the degree of xerostomia with the DAHANCA toxicity scale and was blinded for the EORTC score. Oral cavity, parotid, and submandibular glands (OAR) were delineated on the planning CT according to international guidelines. DVH were extracted from treatment plans. Logistic regression tested the relation between mean doses, patient characteristics, and xerostomia scores. Differences between DVH values and scoring of xerostomia were analyzed with a Kruskal-Wallis test. The relation between xerostomia and dose distributions was further investigated using principal component analysis (PCA). Results: In total, 109 patients were included in the study. A weak correlation was seen between patient and physician-rated toxicity (p = .001), however, in general patients reported more toxicity than physicians. For EORTC score ≥2, the multi-variable analysis was significant for doses to the oral cavity, tobacco status and use of xerogenic medication. Neither the DVH analysis nor the PCA found any clear distinction between xerostomia scores for EORTC or DAHANCA and investigated OARs. Conclusion: Patients tended to report higher scores of xerostomia than the physician. PCA indicated a complex relation between doses to the OAR and xerostomia scores, showing e.g., that reducing doses in one organ was on the expense of increased dose to another organ.

NTCP model validation method for DAHANCA patient selection of protons versus photons in head and neck cancer radiotherapy.

Introduction: Prediction models using logistic regression may perform poorly in external patient cohorts. However, there is a need to standardize and validate models for clinical use. The purpose of this project was to describe a method for validation of external NTCP models used for patient selection in the randomized trial of protons versus photons in head and neck cancer radiotherapy, DAHANCA 35. Material and methods: Organs at risk of 588 patients treated primarily with IMRT in the randomized controlled DAHANCA19 trial were retrospectively contoured according to recent international recommendations. Dose metrics were extracted using MatLab and all clinical parameters were retrieved from the DAHANCA database. The model proposed by Christianen et al. to predict physician-rated dysphagia was validated through the closed testing, where change of the model intercept, slope and individual beta's were tested for significant prediction improvements. Results: Six months prevalence of dysphagia in the validation cohort was 33%. The closed testing procedure for physician-rated dysphagia showed that the Christianen et al. model needed an intercept refitting for the best match for the Danish patients. The intercept update increased the risk of dysphagia for the validation cohort by 7.9 ± 2.5% point. For the raw model performance, the Brier score (mean squared residual) was 0.467, which improved significantly with a new intercept to 0.415. Conclusions: The previously published Dutch dysphagia model needed an intercept update to match the Danish patient cohort. The implementation of a closed testing procedure on the current validation cohort allows quick and efficient validation of external NTCP models for patient selection in the future.

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.

Considerations for study design in the DAHANCA 35 trial of protons versus photons for head and neck cancer.

Proton radiotherapy offers a dosimetric advantage compared to photon therapy in sparing normal tissue, but the clinical evidence for toxicity reductions in the treatment of head and neck cancer is limited. The Danish Head and Neck Cancer Group (DAHANCA) has initiated the DAHANCA 35 randomised trial to clarify the value of proton therapy (NCT04607694). The DAHANCA 35 trial is performed in an enriched population of patients selected by an anticipated benefit of proton therapy to reduce the risk of late dysphagia or xerostomia based on normal tissue complication probability (NTCP) modelling. We present our considerations on the trial design and a test of the selection procedure conducted before initiating the randomised study.

Acute toxicities in proton therapy for head and neck cancer - A matched analysis of the DAHANCA 35 feasibility study.

Background and purpose: As preparation for a national randomized study comparing proton radiotherapy to photon radiotherapy, DAHANCA 35, we performed a non-randomized pilot study to investigate patient selection, logistics, planning, and treatment delivery. With the present study, as a comprehensive safety analysis, we want to compare toxicity during and up to two months after therapy to a historically matched group of patients treated with photon radiotherapy. Materials and methods: 62 patients treated with protons were matched to 124 patients who received photon treatment outside a protocol. Available data were retrieved from the DAHANCA database. Patients were matched on treatment centre, concurrent chemotherapy, tumour site, stage, p16 status for oropharynx cancers. Selection of patients for proton therapy was based on comparative treatment plans with a NTCP reduction for dysphagia and xerostomia at six months. Results: Baseline characteristics between groups were well balanced, except for the type of drug used concurrently; more photon patients received Carboplatin (21.2 % vs 5.8 %, p = 0.01). Proton therapy was associated with significantly less weight loss at the end of treatment, mean weight loss of 3 % for protons and 5 % for photons (p < 0.001). There were more grade 3 skin reactions and grade 3 mucositis after proton treatment compared with photons at the end of treatment, Risk Ratio (RR) 1.9 (95 % CI: 1.01-3.5, p = 0.04) and RR 1.5 (95 % CI: 1.3-1.7, p < 0.001), respectively. All differences resolved at follow up two months after treatment. There were no significant differences between groups on opioid use, use of feeding tubes, or hospitalization during the observation period. Conclusion: Proton treatment resulted in excess objective mucositis and dermatitis, which was transient and did not seem to negatively influence weight or treatment compliance and intensity. Selection bias was likely especially since NTCP models were used for selection of proton treatment and photon treated patients were matched manually. We are currently including patients in a randomized controlled trial.

Selection for proton radiotherapy of grade 1-3 glioma patients.

Background: For adult patients with grade 1-3 gliomas, identifying patients with an indication for proton therapy (PT) can be challenging due to sparse evidence supporting its benefits. In this study, we aimed to ensure national consensus and develop a decision support tool to aid clinicians in identifying patients with grade 1-3 gliomas eligible for PT. Methods: Sixty-one historic patients referred for postoperative radiotherapy for glioma grade 1-3 were included in this study and had new photon therapy and PT plans calculated. These plans along with clinical parameters were presented to neurooncologists with experience in treating brain tumours. The patients were presented at three workshops (WSs), where each neurooncologist individually had to choose between photon and proton therapy. Important parameters were selected using cross validation. Multivariable logistic regression was used to predict the neurooncologists' treatment modality choice. Results: At the three WSs 23, 24 and 19 randomly selected patients were presented. Seventy-five percent of the neurooncologists agreed for 14 patients (61%), 16 patients (67%) and 15 patients (79%) at WS1, WS2 and WS3. Age at radiotherapy and difference in mean dose (ΔDmean) to the residual brain were significant predictors of the choice of treatment modality, p < 0.001. Model coefficients were: ßage = 0.07 per year (95% confidence interval [CI] = 0.05-0.09), and ßΔdose = -0.27 per Gy (95% CI=-0.36--0.18). Conclusion: Higher degree of agreement was reached. Age and ΔDmean to the residual brain significantly predicted the choice of radiation modality. We have developed a decision support model which may aid in the selection of patients with glioma grade 1-3 to PT.

Abnormal glucose tolerance and lung function in children with cystic fibrosis. Comparing oral glucose tolerance test and continuous glucose monitoring.

BACKGROUND: Cystic fibrosis (CF) related diabetes (CFRD) is a common complication of CF. CFRD is associated with declining lung function even before its onset. Regular screening for CFRD using oral glucose tolerance test (OGTT) is recommended. Additionally, continuous glucose monitoring (CGM) has surfaced as a possible surveillance method, but evidence for its use and concordance with OGTT has not been established. METHODS: Children were prospectively recruited at CF center Lund to undergo both intermittent scan CGM (isCGM) and OGTT. Lung function was evaluated by spirometry and multiple breath washout. Demographic and clinical data were collected from the Swedish national CF registry. RESULTS: 32 patients participated in the study, yielding 28 pairs of isCGMs and OGTTs. The OGTTs showed that two patients met the criteria of CFRD, seven had impaired glucose tolerance (IGT) and indeterminate glycemia (INDET) was found in eleven cases. The isCGM percent of measurements >8mmol/L and the number of peaks per day >11 mmol/L have correlations with intermediate OGTT glucose time points, but not the 2hour glucose value. Patients with abnormal glucose tolerance (AGT) had lower lung function than those with normal glucose tolerance demonstrated by both FEV1% predicted and lung clearance index (LCI). CONCLUSION: Correlations can be found between isCGM and OGTT in regards to the latter's intermediate time points. LCI demonstrates as well as FEV1% of predicted, worse lung function in children and adolescents with abnormal glucose tolerance in CF.

Polymorphonuclear leucocytes consume oxygen in sputum from chronic Pseudomonas aeruginosa pneumonia in cystic fibrosis.

BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa is the most severe complication for patients with cystic fibrosis (CF). This infection is characterised by endobronchial mucoid biofilms surrounded by numerous polymorphonuclear leucocytes (PMNs). The mucoid phenotype offers protection against the PMNs, which are in general assumed to mount an active respiratory burst leading to lung tissue deterioration. An ongoing respiratory burst by the PMNs has, however, not been demonstrated previously in endobronchial secretions from chronically infected patients with CF. OBJECTIVE: Based on the accumulating evidence for depletion of molecular oxygen (O(2)) in the mucus in infected CF bronchi, it was hypothesised that the O(2) depletion in the mucus in infected CF bronchi may be accelerated by the respiratory burst of the PMNs due to the reduction of O(2) to the superoxide anion (O(-)(2)) by the phagocyte NADPH oxidase (Phox). METHODS: Methods were established to isolate the O(2) consumption by the respiratory burst from aerobic respiration in freshly expectorated sputum from chronically infected patients with CF. RESULTS: Inhibition of the Phox with diphenylene iodonium (DPI) delayed O(2) depletion, nearly abolished staining of O(-)(2)-producing PMNs with hydroethidine and inhibited the rapid luminol-enhanced chemiluminescence in sputum. Furthermore, the total O(2) consumption was correlated to the concentration of PMNs in the sputum samples. CONCLUSION: The results demonstrate that CF sputum contains PMNs with an active consumption of O(2) for O(-)(2) production and suggest that the respiratory burst is ongoing and causes accelerated O(2) depletion due to formation of O(-)(2) in the lungs of chronically infected patients with CF.

Prediction of radiation-induced mucositis of H&N cancer patients based on a large patient cohort.

PURPOSE/OBJECTIVE: Radiation-induced mucositis is a severe acute side effect, which can jeopardize treatment compliance and cause weight loss during treatment. The study aimed to develop robust models to predict the risk of severe mucositis. MATERIALS/METHODS: Mucosal toxicity scores were prospectively recorded for 802 consecutive Head and Neck (H&N) cancer patients and dichotomised into non-severe event (grade 0-2) and severe event (grade 3+) groups. Two different model approaches were utilised to evaluate the robustness of the models. These used LASSO and Best Subset selection combined with 10-fold cross-validation performed on two-thirds of the patient cohort using principal component analysis of DVHs. The remaining one-third of the patients were used for validation. Model performance was tested through calibration plot and model performance metrics. RESULTS: The main predicted risk factors were treatment acceleration and the first two principal dose components, which reflect the mean dose and the balance between high and low doses to the oral cavity. For the LASSO model, gender and current smoker status were also included in the model. The AUC values of the two models on the validation cohort were 0.797 (95%CI: 0.741-0.857) and 0.808 (95%CI: 0.749-0.859), respectively. The two models predicted very similar risk values with an internal Pearson coefficient of 0.954, indicating their robustness. CONCLUSIONS: Robust prediction models of the risk of severe mucositis have been developed based on information from the entire dose distribution for a large cohort of patients consisting of all patients treated H&N for within our institution over a five year period.

Long-term, low-dose azithromycin treatment reduces the incidence but increases macrolide resistance in Staphylococcus aureus in Danish CF patients.

BACKGROUND: Since 2001, long-term, low-dose azithromycin treatment has been used for CF patients chronically infected with Pseudomonas aeruginosa in the Copenhagen CF centre. Our study investigates changes in incidence of colonization with Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis and changes in macrolide sensitivity in these microorganisms during azithromycin treatment. METHODS: CF patients treated continuously with azithromycin for at least 3 months were included. Results of microbiological examination, including phage typing results of S. aureus, obtained during treatment were compared to results obtained 2 years before treatment. RESULTS: 70 patients (median age 29.1 years) treated for a median of 4 years (range 0.7-5.1) were included. Before treatment, 44 patients had at least one culture positive for S. aureus compared to 25 patients during treatment (p<0.01). Mean percentage of sputum samples with growth of S. aureus decreased from 12.1% (range 0-82.6%) before treatment to 6.1% (range 0-93.2) during treatment (p<0.0006). Prevalence's of H. influenzae and S. pneumoniae also decreased significantly. Fifteen of 214 isolates (7%) of S. aureus were macrolide resistant before treatment, increasing to 95 of 181 isolates (52.5%) during treatment (p<0.001). Macrolide resistant strains were found in 3 of 44 S. aureus colonized patients before treatment and in 11 of 25 patients at some time during treatment (p<0.03), all belonging to different phage types. First resistant S. aureus isolate was isolated after a median treatment duration of 1.5 years (range 0.3-2.9). No MRSA were isolated. Only 1 macrolide resistant isolate of M. catarrhalis was found during treatment. No macrolide resistance was found in H. influenzae or S. pneumoniae. CONCLUSION: Long-term, low-dose treatment with azithromycin in CF patients leads to reduced prevalence of S. aureus, S. pneumoniae, and H. influenzae, but increased macrolide resistance in S. aureus. Reduction in the prevalence of S. aureus will make increasing macrolide resistance clinically insignificant in these patients.

Early aggressive eradication therapy for intermittent Pseudomonas aeruginosa airway colonization in cystic fibrosis patients: 15 years experience.

BACKGROUND: Since 1989, CF-patients intermittently colonized with Pseudomonas aeruginosa have been treated with inhaled colistin and oral ciprofloxacin in the Copenhagen CF-centre. The study evaluates 15 years results of this treatment. METHODS: All isolates of P. aeruginosa from CF-patients intermittently colonized with P. aeruginosa from 1989 to 2003 were identified All anti-P. aeruginosa treatments were evaluated for antibiotics used, treatment duration, pseudomonas-free interval and development of chronic infection. All P. aeruginosa isolates were assessed for resistance and for non-mucoid or mucoid phenotype. RESULTS: 146 CF-patients were included in the study (1106 patient-years). 99 patients had first ever isolate during the study period. Median observation time 7 years (0.1-14.9). 12 patients developed chronic infection. A Kaplan Meyer plot showed protection from chronic infection in up to 80% of patients for up to 15 years. 613 colistin/ciprofloxacin treatments were given. There was no difference in pseudomonas-free interval comparing 3 weeks (5 months) and 3 months (10.4 months) of colistin and ciprofloxacin, but a significant difference compared to no treatment (1.9 months). Patients developing chronic infection had significantly shorter pseudomonas-free interval after treatment of first ever isolate compared to patients remaining intermittently colonized (p<0.003). Treatment failure (P. aeruginosa-positive culture immediately after ended treatment of first ever isolate) was a strong risk factor for development of chronic infection after 3-4 years, OR 5.8. 1093 pseudomonas-isolates were evaluated (86.6% non-mucoid). No colistin-resistance was found. Ciprofloxacin-resistance was found in 4% of isolates. CONCLUSION: Treatment of intermittent P. aeruginosa colonization in CF-patients using colistin and ciprofloxacin can protect up to 80% of patients from development of chronic infection for up to 15 years. A positive culture immediately after treatment of first ever isolate is a strong risk factor for development of chronic infection. We found no colistin-resistance and minimal ciprofloxacin-resistance.

IMRT - Biomarkers for dose escalation, dose de-escalation and personalized medicine in radiotherapy for head and neck cancer.

Radiotherapy (RT) is an integral component in the management of head and neck cancer. Despite progress in several respects, a noteworthy proportion of the treated patients do not achieve complete response after RT. Regardless of novel dose delivery technologies, RT for head and neck cancer is still associated with acute as well as late toxicity. These challenges could potentially be addressed by means of personalized treatment. In this paper, we discuss the possibilities for dose escalation, dose de-escalation and allocation to systemic concomitant treatment based on prognostic and predictive markers for tumor control as well as predictive markers for normal tissue radiosensitivity.

Comparison of multi-institutional pre-treatment verification for VMAT of nasopharynx with delivery errors.

PURPOSE: Measurement-based pre-treatment verification with phantoms frequently uses gamma analysis to assess acceptable delivery accuracy. This study evaluates the sensitivity of a commercial system to simulated machine errors for three different institutions' Volumetric Modulated Arc Therapy (VMAT) planning approaches. METHODS: VMAT plans were generated for ten patients at three institutions using each institution's own protocol (manually-planned at institution 1; auto-planned at institutions 2 and 3). Errors in Multi-Leaf Collimator (MLC) field size (FS), MLC shift (S), and collimator angle (C) of -5, -2, -1, 1, 2 and 5 mm or degrees were introduced. Dose metric constraints discriminated which error magnitudes were considered unacceptable. The smallest magnitude error treatment plans deemed clinically unacceptable (typically for a 5% dose change) were delivered to the ArcCHECK for all institutions, and with a high-dose point ion chamber measurement in 2 institutions. Error detection for different gamma analysis criteria was compared. RESULTS: Not all deliberately introduced VMAT plan errors were detected using a typical 3D 3%/3 mm global gamma pass rate of 95%. Considering all institutions, gamma analysis was least sensitive to negative FS errors. The most sensitive was a 2%/2 mm global analysis for institution 1, whilst for institution 2 it was 3%/3 mm global analysis. The majority of errors (58/59 for institution 1, 54/60 for institution 3) were detected using ArcCHECK and ion chamber measurements combined. CONCLUSIONS: Not all clinically unacceptable errors are detected. Combining ion chamber measurements with gamma analysis improved sensitivity and is recommended. Optimum gamma settings varied across institutions.

Multimodality approaches in the treatment of attention deficit disorders.

This article describes the diagnostic process and various etiologic considerations that underpin the formulation of a comprehensive treatment program for a child with attention deficit disorder and then goes on to describe treatment modalities and strategies. The authors then suggest that the coordinated use of problem-specific treatment modalities is likely to prove more therapeutic and cost-effective than a global treatment.

Health-related quality of life for patients with progressive multiple sclerosis: influence of rehabilitation.

BACKGROUND AND PURPOSE: The health-related quality of life of patients with multiple sclerosis (MS) is an important aspect of care outcome. The purpose of this study was to compare health-related quality of life between patients who received weekly comprehensive outpatient rehabilitation for 1 year and a group that did not receive rehabilitation. SUBJECTS: Twelve patients receiving outpatient care for chronic progressive MS (mean age = 44.5 years, SD = 11.6) were compared with 19 similar patients (mean age = 49.2 years, SD = 9.2) on a waiting list who were not receiving outpatient care. METHODS: A pretest-posttest longitudinal design was used to descriptively compare outcome measures. Multivariate regression analyses were used to determine which variables, controlled for baseline health status and other relevant patient characteristics, were related to the best outcomes at the time of the 1-year follow-up. RESULTS: The treatment group showed improvements in six health status measures on the Rand 36-Item Health Survey 1.0 (SF-36) that were not improved in the wait-listed group. Outpatient treatment was the sole predictor of positive outcome for energy/fatigue (partial R2 = .43) and change in general health (partial R2 = .19). In addition, the treatment group was associated with a positive outcome (together with other independent variables) in the domains of social function and social support. CONCLUSION AND DISCUSSION: Patients with chronic progressive forms of MS appear to derive benefits from an ongoing comprehensive outpatient rehabilitation program. [Di Fabio RP, Choi T, Soderberg J, Hansen CR. Health-related quality of life for patients with progressive multiple sclerosis: influence of rehabilitation.

[Fatal transmural colitis caused by Entamoeba histolytica. Differential diagnosis of chronic inflammatory bowel disease and colon cancer]. / Entamoeba histolyticabetinget transmural colitis med letalt forløb. En differentialdiagnose til kronisk inflammatorisk tarmsygom og cancer coli.

Perforation of the colon is a rare but frequently fatal complication of amoebiasis. We report a case of a 53 year-old male, with no history of travel abroad, who was admitted to hospital with haematochezia. A tumor of the rectum was diagnosed clinically. Due to acute intestinal obstruction, laparotomy was performed, revealing multiple perforations of the large bowel and severe peritonitis leading to subtotal colectomy. The histological examinations revealed transmural amoebic colitis. The patient died due to multi-organ failure.

Achromobacter species in cystic fibrosis: cross-infection caused by indirect patient-to-patient contact.

BACKGROUND AND METHODS: Achromobacter species leads to chronic infection in an increasing number of CF patients. We report 2 cases of Achromobacter ruhlandii cross-infection between patients after well-described indirect contact. RESULTS: Both cases were young, stable, CF patients without chronic infections and with normal FEV1, but experienced clinical deterioration after visits to the home of a CF patient with A. ruhlandii infection and after sharing facilities with an A. ruhlandii infected CF patient on a skiing vacation, respectively. Both cases became positive for A. ruhlandii in airway secretions and were colonized with A. ruhlandii in their sinuses. Aggressive, long-term antibiotic treatment led to clinical stability. One of the cases developed chronic A. ruhlandii infection. CONCLUSION: A. species can cause cross-infection even after a short period of indirect contact between infected and non-infected CF patients. Patients should be followed closely for several months before the possibility of cross-infection is ruled out.

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.