BackgroundIn cystic fibrosis (CF) patients, the upper airways display the same ion channel defect as evident in the lungs, resulting in chronic inflammation and infection. Recognition of the sinonasal area as a site of first and persistent infection with pathogens, such as Pseudomonas aeruginosa, reinforces the “one-airway” hypothesis. Therefore, we assessed the effect of systemic antibiotics against pulmonary pathogens on sinonasal inflammation.MethodsNasal lavage fluid (NLF) from 17 CF patients was longitudinally collected prior to and during elective intravenous (i.v.) antibiotic treatment to reduce pathogen burden and resulting inflammation (median treatment time at time of analysis: 6 days). Samples were assessed microbiologically and cytologically. Cytokine and chemokine expression was measured by Cytometric Bead Array and ELISA (interleukin (IL)-1β, IL-6, IL-8, MPO, MMP9, RANTES and NE). Findings were compared with inflammatory markers from NLF obtained from 52 healthy controls.ResultsInitially, the total cell count of the NLF was significantly higher in CF patients than in controls. However after i.v. antibiotic treatment it decreased to a normal level. Compared with controls, detection frequencies and absolute concentrations of MPO, IL-8, IL-6 and IL-1β were also significantly higher in CF patients. The detection frequency of TNF was also higher. Furthermore, during i.v. therapy sinonasal concentrations of IL-6 decreased significantly (P = 0.0059), while RANTES and MMP9 levels decreased 10-fold and two-fold, respectively. PMN-Elastase, assessed for the first time in NFL, did not change during therapy.ConclusionsAnalysis of NLF inflammatory markers revealed considerable differences between controls and CF patients, with significant changes during systemic i.v. AB treatment within just 6 days. Thus, our data support further investigation into the collection of samples from the epithelial surface of the upper airways by nasal lavage as a potential diagnostic and research tool.

Knowledge of beta-lactam resistance rates in Streptococcus mitis group bacteria is especially important in neutropenic haematological patients as adequate empirical antibiotic treatment (often including agents like meropenem [1]) is paramount. EUCAST guidelines allow one to infer viridans group streptococci (VGS) beta-lactam susceptibility from benzylpenicillin susceptibility; penicillin-resistant isolates should be tested for individual agents. Few studies reported the association between penicillin resistance and broad-spectrum beta-lactam resistance in VGS [2,3], and data from Northern European countries is lacking. Here, we first describe the prevalence of beta-lactam resistance in S. mitis/oralis in The Netherlands. Second, we describe the association between penicillin MIC and broad-spectrum beta-lactam resistance.The Dutch national surveillance system for antimicrobial resistance (ISIS-AR) [4], covering 44 out of 56 Dutch clinical microbiology laboratories in 2017, was searched for susceptibility results of S. mitis/oralis isolates for (benzyl)penicillin, amoxicillin/ampicillin, cefotaxime/ceftriaxone, and meropenem from 2013 through 2017.ISIS-AR collects susceptibility test results of all bacterial isolates of collaborating laboratories. The analysis was limited to the first isolate of each patient. Patients whose first isolate was not tested for penicillin susceptibility were excluded.To avoid bias due to selective testing, for each antibiotic only laboratories testing 50% of isolates were included. Forty-one laboratories were included for analyses on penicillin susceptibility, 24 laboratories for amoxicillin/ampicillin, and 23 for cefotaxime/ceftriaxone. Meropenem was tested in 15 laboratories; here the inclusion rule was not applied, as this resulted in a significant impact on the number of isolates for analysis. All selected laboratories used EUCAST guidelines, except one laboratory in 2013. MIC breakpoint for susceptibility is 0.25 mg/L for penicillin, 0.5 mg/L for amoxicillin/ampicillin and cefotaxime/ceftriaxone, and 2 mg/L for meropenem.Of 4164 S. mitis/oralis isolates tested for penicillin, 3634 were reported susceptible (87.2%), 281 intermediate (6.7%), and 249 resistant (6.0%). Of 2019 isolates with amoxicillin/ampicillin susceptibility reported, 117 isolates were reported resistant (5.8%) to either agent. Of 2079 isolates with cefotaxime/ceftriaxone susceptibility reported, 159 were resistant (7.6%). Of 306 isolates with meropenem susceptibility reported, four were resistant (1.3%). Percentages of broad-spectrum beta-lactam resistance by penicillin susceptibility category is shown in the Table S1.For amoxicillin/ampicillin susceptible isolates, the median penicillin MIC with automated testing was 0.06 mg/L (IQR 0.06e0.12; n ¼ 875), for intermediate isolates 1.0 mg/L (IQR 0.5e2.0; n ¼ 55), and for resistant isolates 2.0 mg/L (IQR 2.0e4.0; n ¼ 51). Results with gradient testing were similar: for susceptible isolates median penicillin MIC was 0.047 mg/L (IQR 0.023e0.094; n ¼ 327), for intermediat...

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