Incidence of patients with non-cystic fibrosis bronchiectasis in Germany - A healthcare insurance claims data analysis.

BACKGROUND: Incidence and prevalence of patients with non-cystic fibrosis bronchiectasis (NCFB) appear to be increasing worldwide but supporting epidemiological data are scarce. This study assesses the incidence of NCFB patients in Germany in 2013 and analyzes comorbidities and basic patterns of resource use. METHODS: A representative sample of 3.988.648 anonymized persons covered by German public statutory health insurances was used to identify incident patients with NCFB in 2013. RESULTS: After extrapolation to the general population of the 728 patients found in the reference insurance database, we estimate that a total of 17,095 NCFB patients were newly diagnosed across the country in 2013 as having NCFB. This corresponds to an incidence of 21.23 per 100.000 inhabitants. The majority of NCFB patients (98.4%) was at least 18 years old, and 52.7% of the NCFB patients were male. Trend analysis shows a rise of NCFB incidence in Germany from 2011 through 2013. COPD (41.4%), asthma (32.8%) and gastroesophageal reflux (18.3%) were the most frequent predisposing conditions. Coronary heart disease was observed in more than one quarter of NCFB patients (28.2%). 58.4% of the NCFB outpatients received antiobstructive inhalative medication. Of the adult NCFB patients, 51.6% were prescribed antibiotics to treat NCFB by settled doctors (outpatient treatment); 51.5% of those patients were males. The peak of antibiotic treatment was observed in the 75-79 age group for males and 70-74 and 75-79 years for females. The majority of diagnosed patients (54.1%) received at least two prescriptions during 2013. Bacterial pathogens were coded for a total of 10.7% of NCFB patients, while Pseudomonas aeruginosa was only documented in 2.3%. Among those diagnosed in 2013, 8.0% of the adult NCFB patients who received antibiotic treatment had to be hospitalized. CONCLUSIONS: Although hospital admissions due to exacerbation in the first year of diagnosing NCFB are not rare, outpatient burden and costs must also be considered a major part of care. Given the increasing recognition of NCFB, a better understanding of the economic burden of the disease is required, with a view towards improving patient management. For this, more detailed, prospective studies are needed.

Susceptibility patterns of bacterial isolates from hospitalised patients with respiratory tract infections (MOXIAKTIV Study).

The objective of this study was to determine: (i) the prevalence of resistance in current clinical isolates of Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis and Klebsiella pneumoniae; (ii) the prevalence of production of extended-spectrum beta-lactamases (ESBLs) and methicillin resistance in S. aureus; and (iii) regional differences in the prevalence of ESBL production and clonality of K. pneumoniae isolates. Pathogens causing respiratory tract infections in hospitalised patients were prospectively collected from all over Germany. Drugs tested by Etest included moxifloxacin, levofloxacin, amoxicillin/clavulanic acid, cefuroxime, clarithromycin and penicillin G. ESBL production by K. pneumoniae was determined using cefotaxime/ceftazidime +/- clavulanic acid. Deutsches Institut für Normung (German Institute for Standardisation)/European Committee on Antimicrobial Susceptibility Testing (DIN/EUCAST) breakpoints were used where applicable. Overall, 1859 pathogens were analysed. For all species tested the fluoroquinolones achieved the highest overall susceptibility rate (92.8%) compared with clarithromycin (60.5%), amoxicillin/clavulanic acid (85.7%) and cefuroxime (89.6%). From 438 K. pneumoniae isolates, 13.0% produced an ESBL. The ESBL prevalence was 38.8% in Eastern Germany with a trend towards clonality in some centres, but ranged from 4.7% to 7.1% in Southern, Northern and Western Germany. Among the methicillin-susceptible S. aureus isolates, 10.1% were moxifloxacin- and levofloxacin-resistant. Of the S. pneumoniae isolates, 99.3% were moxifloxacin- and levofloxacin-susceptible, 93.9% were penicillin G-susceptible and 85.7% were clarithromycin-susceptible. With a MIC90 value (minimal inhibitory concentration for 90% of the isolates) of 0.19 mg/L, moxifloxacin was more potent than levofloxacin (MIC90 = 1 mg/L) against S. pneumoniae. Haemophilus influenzae and M. catarrhalis were almost 100% susceptible to the quinolones; 100% of the M. catarrhalis but only 4.5% of the H. influenzae strains were clarithromycin-susceptible. Moxifloxacin was the most active agent amongst the drugs tested, in particular against Gram-positive pathogens.

Moxifloxacin and azithromycin but not amoxicillin protect human respiratory epithelial cells against streptococcus pneumoniae in vitro when administered up to 6 hours after challenge.

We determined the protective effect of moxifloxacin, azithromycin, and amoxicillin against Streptococcus pneumoniae infection of respiratory cells. Moxifloxacin and azithromycin effectively killed intracellular S. pneumoniae strains and protected respiratory epithelial cells significantly even when given 6 h after S. pneumoniae challenge. Amoxicillin was less effective.

The signal transducer encoded by ampG is essential for induction of chromosomal AmpC beta-lactamase in Escherichia coli by beta-lactam antibiotics and 'unspecific' inducers.

Chemical mutagenesis of the AmpC beta-lactamase-hyperinducible Escherichia coli strain SN0301/pNu305 carrying the cloned ampC and ampR genes from Citrobacter freundii OS60 gave four independent mutants in which beta-lactamase was no longer inducible, or was inducible only to a low level, by beta-lactam antibiotics. The genes ampC, ampR, ampD and ampE, which were essential for beta-lactamase induction, were functional in these mutants. In all four mutants, the sites of mutation were mapped to 9.9 min on the E. coli chromosome. Complementation with wild-type ampG restored inducibility of beta-lactamase to wild-type levels. The nucleotide sequence of all four mutant ampG alleles (ampG1, ampG3, ampG4 and ampG5) was determined. In three of the mutants, a single base exchange led to an amino acid change from glycine to aspartate at different sites in the deduced amino acid sequence. In the fourth mutant (ampG4), with low-level inducibility, the nucleotide sequence was identical to wild-type ampG. Spontaneous back-mutation of the chromosomal ampG1 mutant resulted in restoration of wild-type inducibility and a return to the wild-type ampG sequence. Unspecific induction by components of the growth medium was also dependent on intact ampG function.