Background
Chronic kidney disease (CKD) still leads to high mortality rates, mainly due to cardiovascular disease. One important influencing factor is persisting low-grade chronic inflammation partly ...maintained by gingivitis that favors transient bacteremia during daily activities such as toothbrushing.
Methods
To examine whether intensive dental prophylaxis can restore oral health, reduce the prevalence of bacteremia and degree of systemic inflammation indicated by CRP levels, we conducted this pilot study examining 30 CKD patients aged 6–26 years, 15 receiving intensive prophylaxis (IP), 15 receiving treatment as usual (TAU) serving as control group. There were three appointments for examination, each 10 ± 1 weeks apart (at baseline, after intervention periods one and two, when TAU also received IP, and the IP group stopped prophylaxis).
Results
The gingival index (GI) in the IP group decreased by 90% (GI 0.09; p=0.001), resulting in almost healthy gingiva. There was no significant change in CRP or prevalence of bacteremia. General prevalence of bacteremia after toothbrushing was 9.5% affecting 7 (26%) of the participants. In three participants, bacteremia dissolved after IP, in one after TAU. Two patients developed bacteremia ≥ 10 weeks after ending IP. We identified eight different bacterial species.
Conclusions
We were able to show that IP can effectively treat gingivitis. It might be a promising approach to reduce systemic inflammation and subsequently lower premature cardiovascular disease, despite the lack of statistical significance. Future research requires a larger patient cohort to enable matched treatment groups with long-term follow-up and molecular detection methods for bacteremia.
Graphical abstract
A higher resolution version of the Graphical abstract is available as Supplementary information
Antimicrobial treatment options for mycobacterial infections are limited due to intrinsic resistance and the emergence of acquired resistance in
Mycobacterium tuberculosis
. Isolates resisting first- ...and second line drugs are raising concerns about untreatable infections and make the development of new therapeutic strategies more pressing. Nitroxoline is an old oral antimicrobial that is currently repurposed for the treatment of urinary tract infection (UTI). In this study, we report the
in vitro
activity of nitroxoline against 18 clinical isolates of
M. tuberculosis
complex (MTBC) (
M. tuberculosis
N = 16,
M. bovis
BCG N = 1,
M. bovis
sp.
bovis
N = 1). Since nitroxoline achieves high concentrations in the urinary tract, we included all MTBC-isolates from urinary samples sent to our laboratory between 2008 and 2021 (University Hospital of Cologne, Germany). Isolates from other sources (N = 7/18) were added for higher sample size and for inclusion of drug-resistant
M. tuberculosis
isolates (N = 4/18). Based on our clinical routine the fluorescence-based liquid media system BACTEC MGIT 960 was used for susceptibility testing of nitroxoline and mainstay antitubercular drugs. Nitroxoline yielded a MIC
90
of 4 mg/L for MTBC. In all
M. tuberculosis
isolates nitroxoline MICs were at least two twofold dilutions below the current EUCAST susceptibility breakpoint of ≤16 mg/L (limited to
E. coli
and uncomplicated UTI).
In vitro
activity of nitroxoline can be considered excellent, even in multidrug-resistant isolates. Future studies with
in vivo
models should evaluate a potential role of nitroxoline in the treatment of tuberculosis in the era of drug resistance.
The shiga toxin-producing E. coli (STEC) O104:H4 caused a major outbreak in Germany in spring 2011. STEC are usually susceptible to common antibiotics. However, antibiotic treatment of STEC-infected ...patients is not recommended because STEC may enhance production and release of shiga toxins (STX) in response to antibiotics, which eventually enhances the frequency and severity of clinical symptoms, including haemolytic uraemic syndrome (HUS) and fatalities.
We characterized the response to antibiotics of STEC O104:H4 isolates from two HUS patients during the German STEC outbreak in spring 2011 in comparison to the common STEC O157:H7. Liquid cultures of STEC O157:H7 and O104:H4 were incubated with graded dilutions of the antibiotics ciprofloxacin, meropenem, fosfomycin, gentamicin, rifampicin, and chloramphenicol. At defined times of antibiotic treatment, transcriptional activation of the STX2 gene, contents of STX and STX-activity in the culture supernatants were quantified. Unlike the common serotype O157:H7, STEC O104:H4 does not release STX in response to therapeutic concentrations of ciprofloxacin, meropenem, fosfomycin, and chloramphenicol.
In future outbreaks, the response of the respective epidemiologic STEC strain to antibiotics should be rapidly characterized in order to identify antibiotics that do not enhance the release of STX. This will eventually allow clinical studies tackling the question whether antibiotic treatment impacts on the eradication of STEC, clinical course of disease, and frequency of carriers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Identification of antimycobacterial activity against nontuberculous mycobacteria of nitroxoline•Nitroxoline already approved for other infections with an established safety profile•Excellent in ...vitro activity against molecularly characterized clinical isolates of the Mycobacterium abscessus complex with antimicrobial resistance to currently used drugs.•Potential of repurposed use of nitroxoline because infections by mycobacteria are increasingly reported worldwide but too few novel drugs are being developed
The old antimicrobial nitroxoline is approved to treat urinary tract infection (UTI) and is currently rediscovered for treatment of drug resistant pathogens. Mycobacteria of the Mycobacterium abscessus complex (MYABS) are rapid-growing nontuberculous mycobacteria that are associated with difficult to treat infections of the lungs in patients with pulmonary disorders such as cystic fibrosis. In this study we assessed the in vitro activity of nitroxoline against molecularly characterized drug-resistant MYABS isolates from clinical samples to address potential repurposing of nitroxoline in difficult-to-treat MYABS infection.
The isolates originated from clinical samples collected between 2010 and 2019 at the University Hospital of Cologne, Germany (N=16; 10/16 M. abscessus Spp. abscessus, 4/16 M. abscessus Spp. massiliense, 2/16 M. abscessus Spp. bolletii). Nitroxoline activity was compared to standard antimicrobials recommended for treatment of MYABS infection. For drug susceptibility testing of nitroxoline and comparators broth microdilution was performed based on current Clinical and Laboratory Standards Institute (CLSI) guidelines.
Nitroxoline yielded a MIC90 of 4 mg/L (range 2–4 mg/L), which is two twofold dilutions below the current EUCAST susceptibility breakpoint of ≤ 16 mg/L (limited to uncomplicated UTI and Escherichia coli). Resistance to other antimicrobials was common in our cohort (16/16 isolates resistant to ciprofloxacin, imipenem and doxycycline; 12/16 isolates resistant to tobramycin; 9/16 isolates resistant to cefoxitin; 7/16 isolates resistant to clarithromycin; 2/16 isolates resistant to amikacin).
Nitroxoline has a promising in vitro activity against drug-resistant MYABS isolates. Future studies should investigate this finding with macrophage and in vivo models.
In October 2016, an adolescent boy sought care for acute genital ulceration in Cologne, Germany. We presumed a sexually transmitted infection, but initial diagnostic procedures yielded negative ...results. He was hospitalized because swab samples from the lesion grew toxigenic Corynebacterium diphtheriae, leading to the diagnosis of possibly sexually transmitted cutaneous diphtheria.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
With 1.5 million deaths worldwide in 2018, tuberculosis (TB) remains a major global public health problem. While pulmonary TB (PTB) is the most common manifestation, the proportion of ...extrapulmonary TB (EPTB) is increasing in low-burden countries. EPTB is a heterogeneous disease entity posing diagnostic and management challenges due to the lack of reliable biomarkers. In this study, we prospectively evaluated clinical data and treatment response which were correlated with different biomarkers.
Methods
The study was conducted at the University Hospital of Cologne. 20 patients with EPTB were enrolled. We analyzed plasma interferon-γ-inducible protein 10 (IP-10) levels in plasma by ELISA for up to 12 months of treatment. In addition, the QuantiFERON
®
-TB Gold Plus (QFT
®
Plus) test was performed during the course of treatment. Clinical data were assessed prospectively and correlated with QFT
®
Plus and IP-10 levels.
Results
Plasma IP-10 levels were found to be significantly increased (
p
< 0.001) in patients with extensive disease compared to patients with limited disease (cervical lymph node TB) or healthy controls. In patients with clinically confirmed paradoxical reaction (PR), a further increase of IP-10 was noted. IFN-γ measured by the QFT
®
Plus test did not decrease significantly during the course of treatment. Of note, in four EPTB patients (20%) without radiographic pulmonary involvement, sputum culture was positive for
Mycobacterium tuberculosis
.
Conclusion
Our data demonstrate that IP-10 may be a valuable biomarker for estimation of disease severity in EPTB and monitoring of the disease course in extensive forms. However, IP-10 may be less suitable for diagnosis and monitoring of EPTB patients with limited disease. The QFT
®
Plus test does not appear to be a suitable marker for therapy monitoring. Sputum should be examined in EPTB patients even in case of normal diagnostic imaging of the chest.
is an emerging pathogen with resistance to many commonly used antifungal agents. Infections with
require rapid and reliable detection methods to initiate successful medical treatment and contain ...hospital outbreaks. Conventional identification methods are prone to errors and can lead to misidentifications. PCR-based assays, in turn, can provide reliable results with low turnaround times. However, only limited data are available on the performance of commercially available assays for
detection. In the present study, the two commercially available PCR assays
ID (OLM, Newcastle Upon Tyne, UK) and Fungiplex
RUO Real-Time PCR (Bruker, Bremen, Germany) were challenged with 29
isolates from all five clades and eight other
species as controls.
ID reliably detected
with a limit of detection (LoD) of 1 genome copies/reaction. However, false positive results were obtained with high DNA amounts of the closely related species
and
. The Fungiplex
RUO Real-Time PCR kit detected
with an LoD of 9 copies/reaction. No false positive results were obtained with this assay. In addition,
could also be detected in human blood samples spiked with pure fungal cultures by both kits. In summary, both kits could detect
-DNA at low DNA concentrations but differed slightly in their limits of detection and specificity.
The spectrum of primary hyperoxaluria type I is extremely heterogeneous, ranging from singular to recurrent urolithiasis and early end-stage renal disease (ESRD). In infantile oxalosis, the most ...devastating form, ESRD occurs as early as within the first weeks of life. No kidney replacement therapy sufficiently removes endogenously overproduced oxalate. However, curative combined liver-kidney transplant often is impracticable in small infants. Oxalobacter formigenes (O formigenes) , an anaerobic oxalate-degrading bacterium, is a colonizer of the healthy human colon. Oral administration of O formigenes has been shown to significantly decrease urine and plasma oxalate levels in patients with primary hyperoxaluria. We report compassionate use of O formigenes in two 11-month-old girls with infantile oxalosis and ESRD. They received O formigenes twice a day for 4 weeks (or until transplant). Dialysis regimens were unchanged. Plasma oxalate levels decreased from >110 μmol/L before to 71.53 μmol/L under treatment in patient 1 and from >90 to 68.56 μmol/L (first treatment period) and 50.05 μmol/L (second treatment period) in patient 2. O formigenes was well tolerated. No serious side effects were reported. Extremely increased plasma oxalate levels in patients with infantile oxalosis may enable intestinal elimination of endogenous oxalate in the presence of O formigenes . Therefore, O formigenes therapy may be helpful as a bridging procedure until transplant in such patients.
On examination she looked well, with temperature 36·6°C, pulse 80 beats per min, and blood pressure 110/60 mm Hg. N meningitidis is a commensal of the human upper respiratory tract in more than 8% of ...the adult population worldwide. The main active part of the LOS is the Lipid A moiety, which contains six fatty acyl chains in the most active form.3 The enzyme for the acylation of Lipid A is encoded in the lpxL1-gene, and mutations in this gene result in an underacylated and therefore inactivated Lipid A.4 Because chronic meningococcaemia is associated with lpxL1 mutations in N meningitidis we sequenced the lpxL1-region in our isolate P3485 and identified eight point mutations causing changes in the aminoacid sequence of the lpxL1 gene (appendix).4 We showed that cytokine induction in the host was decreased by our isolate, evidenced by reduced induction of phospho p38 MAPK, phospho NFκB, and IL-6 in human macrophages (appendix).
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