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Gut Pathogens Apr 2021Helicobacter cinaedi are motile, gram-negative spiral rods with a natural reservoir in the intestinal tract of hamsters and rhesus monkeys. In humans, H. cinaedi has...
BACKGROUND
Helicobacter cinaedi are motile, gram-negative spiral rods with a natural reservoir in the intestinal tract of hamsters and rhesus monkeys. In humans, H. cinaedi has been reported in different human infections like fever, abdominal pain, gastroenteritis, proctitis, diarrhoea, erysipelas, cellulitis, arthritis, and neonatal meningitis typically diagnosed by positive blood cultures. Even though H. cinaedi has been detected from human blood and stool the entry of H. cinaedi into the blood stream was undocumented until quite recently. The use of pulse-field gel electrophoresis (PFGE) demonstrated that stool- and blood-derived H. cinaedi strains were consistent.
CASE PRESENTATION
Here, we describe a rare Danish case of H. cinaedi bacteraemia in an immunocompetent 44-year-old male with diarrhoea. We isolated H. cinaedi from a blood culture taken at admission, and from a FecalSwab taken at day six despite ongoing antibiotic therapy. Next, we made a genetic comparison of both isolates by use of Multi-locus sequence typing (MLST)- and Single nucleotide polymorphism (SNP)-analysis. The two isolates were identical with zero SNPs and by use of MLST the isolate was identified as a novel ST20, confirming previous data of the intestinal tract as a route of H. cinaedi bacteraemia. The results of our AST showed a resistance pattern with higher MICs for ciprofloxacin and clarithromycin than for ampicillin, amoxicillin, gentamicin, and imipenem. The patient was cured with targeted therapy with pivampicillin; however, the primary source of transmission was unknown.
CONCLUSIONS
In conclusion, this case of H. cinaedi bacteraemia secondary to enterocolitis in an immunocompetent patient provide clear evidence that one route of infection occurs through translocation from the intestinal tract to the bloodstream. Helicobacter cinaedi from blood and faeces were identical with a novel ST20, resistant to ciprofloxacin and clarithromycin however, the patient was cured with oral pivampicillin.
PubMed: 33888153
DOI: 10.1186/s13099-021-00422-8 -
International Archives of Allergy and... 2021Intradermal testing with delayed reading (IDTdr), used routinely in many centers, may identify delayed reactions to penicillins. However, few studies have compared the...
BACKGROUND
Intradermal testing with delayed reading (IDTdr), used routinely in many centers, may identify delayed reactions to penicillins. However, few studies have compared the results of IDTdr with drug provocation test (DPT). The aim of this study was to examine the proportion of provocation-positive patients testing positive on IDTdr.
METHODS
Fifty-seven patients with a positive DPT occurring >2 h after intake of penicillin V, dicloxacillin, pivampicillin, or amoxicillin had an IDTdr with penicillin G, amoxicillin, ampicillin, and dicloxacillin. A control group included 18 patients with negative DPTs with the suspected penicillin.
RESULTS
In total 25% (n = 14) of provocation-positive patients tested positive on IDTdr. Among patients with positive IDTdr, 9/14 (64%) versus 11/43 (26%) in the IDTdr negative group (p < 0.05) had required oral steroids to treat skin reactions following DPT. No other differences between IDTdr positive and negative groups were found. No controls had a positive IDTdr.
CONCLUSION
Investigating with IDTdr would have identified 25% of patients with a DPT-verified allergy with delayed reactions. It is difficult to target subgroups who will test positive on IDTdr. There were more patients who tested positive on IDT who had received oral steroids after DPT, and this may be an indication that skin reaction severity plays a role in skin testing diagnostics. Further potential predictors for positivity of IDTdr, such as duration of skin symptoms, should be assessed in large studies in order to optimize the investigations of nonimmediate drug allergic reactions.
Topics: Anti-Bacterial Agents; Drug Hypersensitivity; Humans; Hypersensitivity, Delayed; Penicillin G; Penicillins; Skin Tests; Symptom Assessment
PubMed: 33873191
DOI: 10.1159/000515080 -
Journal of Cellular Biochemistry Dec 2020Circular RNA (circRNA) has been reported to have great scientific significance and clinical value in multiple cancers including colorectal cancer (CRC). However, the...
Circular RNA (circRNA) has been reported to have great scientific significance and clinical value in multiple cancers including colorectal cancer (CRC). However, the biological function of most circRNAs in CRC is still in its infancy. Herein, we discovered the differential expressed circRNAs (DECs) between CRC tissues and matched adjacent using deep RNA sequencing and further confirmed the DECs expression by combining with another Gene Expression Omnibus dataset. Furthermore, we validated the expression of the top four upregulated circRNAs (hsa_circ_0030632, hsa_circ_0004887, hsa_circ_0001550, and hsa_circ_0001681) in both of paired CRC tissues and CRC cell lines. Then, a circRNA/microRNA/messenger RNA regulatory network was established and the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed these four circRNAs participated in various biological processed including apoptotic process and multiple metabolic processes. Moreover, based on the regulatory network, three bioactive compounds (pergolide, pivampicillin, and methylergometrine) for the treatment of CRC were also found. In conclusion, this study improved our understanding of circRNAs and may also facilitate the finding of promising targets and biomarkers in CRC.
PubMed: 32115780
DOI: 10.1002/jcb.29703 -
American Journal of Obstetrics and... Dec 2019Antibiotics are commonly prescribed during pregnancy. Although the safety of most penicillins is well established, some controversy and uncertainty are associated with...
BACKGROUND
Antibiotics are commonly prescribed during pregnancy. Although the safety of most penicillins is well established, some controversy and uncertainty are associated with the use of other commonly prescribed antibiotics.
OBJECTIVE
To determine the risk of congenital malformations following first-trimester in utero exposure to 10 commonly prescribed antibiotics in Denmark.
MATERIALS AND METHODS
This was a cohort study comprising all singleton liveborn children in Denmark between 2000 and 2015. Data on malformations were collected through 2016. Merging validated and comprehensive populationwide Danish healthcare and civic registries, we merged data on pregnancy, prescription drugs purchases during first trimester and congenital malformations. Using logistic regression, we calculated the odds ratio for congenital malformations (any), major congenital malformations, and cardiac congenital malformations for the 10 most commonly prescribed antibiotics (excluding 4 penicillins that served as control). In the primary analysis, the exposed cohort was compared to a cohort exposed to any of 4 penicillins considered safe during pregnancy (ampicillin, pivampicillin, benzylpenicillin, and phenoxymethylpenicillin). In sensitivity analysis, the exposed cohort was compared to an unexposed cohort. Covariate adjustments were made for maternal age at delivery, year of delivery, parity, pre-pregnancy body mass index, smoking, educational status, employment status, and annual personal income.
RESULTS
We found no increased risk of congenital malformations to be related to first-trimester in utero exposure to the 10 most commonly prescribed antibiotics in Denmark compared to a cohort of pregnant women exposed to penicillins that are considered safe during pregnancy. Compared to unexposed pregnancies, small increased risks for major malformations and cardiac malformations were apparent for pivmecillinam (odds ratio, 1.13; confidence interval, 1.06-1.19; and odds ratio, 1.15; confidence interval, 1.04-1.28, respectively), sulfamethizole (odds ratio, 1.15; confidence interval, 1.07-1.24; and odds ratio, 1.22; confidence interval, 1.07-1.39, respectively), and azithromycin (odds ratio, 1.19, confidence interval, 1.03-1.38; and odds ratio, 1.29, confidence interval, 0.99-1.67, respectively).
CONCLUSION
In this large populationwide cohort study, we found, with a high degree of precision, no increased risk of congenital malformations following first-trimester exposure to 10 commonly prescribed systemic antibiotics.
Topics: Adult; Amdinocillin Pivoxil; Anti-Bacterial Agents; Azithromycin; Case-Control Studies; Cohort Studies; Congenital Abnormalities; Denmark; Educational Status; Employment; Female; Heart Defects, Congenital; Humans; Logistic Models; Maternal Age; Maternal Exposure; Obesity, Maternal; Odds Ratio; Penicillins; Pregnancy; Pregnancy Trimester, First; Smoking; Sulfamethizole; Young Adult
PubMed: 31260651
DOI: 10.1016/j.ajog.2019.06.050 -
Molecules (Basel, Switzerland) Feb 2019The problem of determining the formation of complexes of β-lactam antibiotics with cyclodextrins (CDs) and the interactions involved in this process were addressed by...
The problem of determining the formation of complexes of β-lactam antibiotics with cyclodextrins (CDs) and the interactions involved in this process were addressed by machine learning on multispectral images. Complexes of β-lactam antibiotics, including cefuroxime axetil, cefetamet pivoxil, and pivampicillin, as well as CDs, including αCD, βCD, γCD, hydroxypropyl-αCD, methyl-βCD, hydroxypropyl-βCD, and hydroxypropyl-γCD, were prepared in all combinations. Thermograms confirming the formation of cyclodextrin complexes were obtained using differential scanning calorimetry. Transmission Fourier-transform infrared (tFTIR) and complementary attenuated total reflectance FTIR (ATR) coupled with machine learning were techniques chosen as a nondestructive alternative. The machine learning algorithm was used to determine the formation of complexes in samples using solely their tFTIR and ATR spectra at the prediction stage. Parameterized method 7 (PM7) was used to support the analysis by molecular modeling of the complexes. The model developed through machine learning properly distinguished samples with formed complexes form noncomplexed samples with a cross-validation accuracy of 90.4%. Analysis of the contribution of spectral bands to the model indicated interactions of ester groups of β-lactam antibiotics with CDs, as well as some interactions of cephem ring in cefetamet pivoxil and penam moiety in pivampicillin. Molecular modeling with PM7 helped to explain experimental results and allowed to propose possible binding modes.
Topics: Cyclodextrins; Machine Learning; Models, Molecular; Molecular Conformation; Spectrum Analysis; Structure-Activity Relationship; beta-Lactams
PubMed: 30791432
DOI: 10.3390/molecules24040743 -
Molecular Diagnosis & Therapy Jun 2018Isocitrate dehydrogenase 1 (IDH1) is a dimeric enzyme responsible for supplying the cell's nicotinamide adenine dinucleotide phosphate (NADPH) reserves via...
BACKGROUND
Isocitrate dehydrogenase 1 (IDH1) is a dimeric enzyme responsible for supplying the cell's nicotinamide adenine dinucleotide phosphate (NADPH) reserves via dehydrogenation of isocitrate (ICT) and reduction of NADP+. Mutations in position R132 trigger cancer by enabling IDH1 to produce D-2-hydroxyglutarate (2-HG) and reduce inhibition by ICT. Mutant IDH1 can be found as a homodimer or a heterodimer.
OBJECTIVE
We propose a novel strategy to inhibit IDH1 R132 variants as a means not to decrease the concentration of 2-HG but to provoke a cytotoxic effect, as the cell malignancy at this point no longer depends on 2-HG. We aim to inhibit the activity of the mutant heterodimer to block the wild-type subunit. Limiting the NADPH reserves in a cancerous cell will enhance its susceptibility to the oxidative stress provoked by chemotherapy.
METHODS
We performed a virtual screening using all US FDA-approved drugs to replicate the loss of inhibition of mutant IDH1 by ICT. We characterized our results based on molecular interactions and correlated them with the described phenotypes.
RESULTS
We replicated the loss of inhibition by ICT in mutant IDH1. We identified 20 drugs with the potential to inhibit the heterodimeric isoform. Six of them are used in cancer treatment.
CONCLUSIONS
We present 20 FDA-approved drugs with the potential to inhibit IDH1 wild-type activity in mutated cells. We believe this work may provide important insights into current and new approaches to dealing with IDH1 mutations. In addition, it may be used as a basis for additional studies centered on drugs presenting differential sensitivities to different IDH1 isoforms.
Topics: Amino Acid Sequence; Antineoplastic Agents; Binding Sites; Dasatinib; Dihydroergotamine; Enzyme Inhibitors; Epirubicin; Gene Expression; High-Throughput Screening Assays; Humans; Indazoles; Indoles; Isocitrate Dehydrogenase; Molecular Docking Simulation; Mutation; Phenylcarbamates; Pivampicillin; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Protein Multimerization; Pyrimidines; Sulfonamides; Thermodynamics; Tosyl Compounds; User-Computer Interface
PubMed: 29651790
DOI: 10.1007/s40291-018-0331-2 -
BMJ Case Reports Sep 2015Good's syndrome is a rare primary immunodeficiency associated with adult thymoma. Complications are mainly autoimmune manifestations and recurrent infections with...
Good's syndrome is a rare primary immunodeficiency associated with adult thymoma. Complications are mainly autoimmune manifestations and recurrent infections with encapsulated bacteria. Only one possible case of combined granulomatous-lymphocytic interstitial lung disease (GL-ILD) and Good's syndrome have been described earlier, but the patient died at the time of diagnosis. This is the first case of GL-ILD in Good's syndrome with a successful outcome. We present a case of a 43-year-old man with GL-ILD, who suffered from recurrent infections of Haemophilus influenzae and Pneumocystis jirovecii, with 8-year follow-up. After a thymectomy, he was diagnosed with Good's syndrome and GL-ILD. He was treated with prophylactic pivampicillin, quinolones and cephalosporins for his recurrent P. jirovecii and H. influenzae infections, an approach that proved unsuccessful due to resistance, with relapse after cessation. He was stabilised with oral diaminodiphenyl-sulfone for P. jirovecii and colistimethate-sodium inhalations for H. influenzae, which is a new approach to prophylactic treatment.
Topics: Adult; Agammaglobulinemia; Anti-Bacterial Agents; Cephalosporins; Granuloma; Haemophilus Infections; Haemophilus influenzae; Humans; Immunologic Deficiency Syndromes; Lung Diseases, Interstitial; Male; Neoplasms, Glandular and Epithelial; Pivampicillin; Pneumocystis Infections; Pneumocystis carinii; Quinolones; Rare Diseases; Thymoma; Thymus Neoplasms
PubMed: 26424818
DOI: 10.1136/bcr-2014-205635 -
BMJ Case Reports Jul 2015We present a case report of a 65-year-old man admitted to the department of infectious diseases on suspicion of meningitis with headache, fever and double vision. A...
We present a case report of a 65-year-old man admitted to the department of infectious diseases on suspicion of meningitis with headache, fever and double vision. A cerebral MRI revealed a 17×30 mm pontine abscess with surrounding oedema. The patient had, 2 months prior to admission, been treated for Streptococcus salivarius aortic valve endocarditis. The abscess was not suitable for surgery, and the patient received multidrug antibiotic treatment for 4 weeks. The patient initially responded well clinically, but was readmitted 4 weeks after discontinuation of treatment, with headache and dizziness. A new cerebral MRI showed progression of the abscess. He received an additional 8 weeks of broad spectrum antibiotic treatment, followed by 12 weeks of oral treatment with pivampicillin. His symptoms resolved and a cerebral MRI at discontinuation of treatment showed regression of the abscess to 7.5 mm.
Topics: Aged; Anti-Bacterial Agents; Aortic Valve; Bicuspid Aortic Valve Disease; Brain Abscess; Drug Therapy, Combination; Endocarditis, Bacterial; Heart Defects, Congenital; Heart Valve Diseases; Humans; Magnetic Resonance Imaging; Male; Multimodal Imaging; Positron-Emission Tomography; Streptococcal Infections; Treatment Outcome
PubMed: 26139646
DOI: 10.1136/bcr-2014-205949 -
Przeglad Epidemiologiczny 2014The Polish results of the international Happy Audit 2 project are reported which objective was to present therapeutic decisions made by general practitioners (especially... (Comparative Study)
Comparative Study
OBJECTIVE
The Polish results of the international Happy Audit 2 project are reported which objective was to present therapeutic decisions made by general practitioners (especially antibiotics prescribed) and diagnostic methods applied to patients with respiratory tract infections (RTI).
MATERIAL AND METHODS
[corrected] Following each visit of patient with respiratory tract infection, general practitioners participating in the study completed the questionnaire. The questionnaire included patient's data (age, gender), the duration of disease, clinical symptoms, diagnosis, prescribed antibiotics, additional testing as well as the influence of various factors on therapeutic decision.
RESULTS
Having considered the results of HappyAudit in Poland, a total of 5,137 office visits of patients reporting symptoms of RTIs were analyzed. The average duration of symptoms before visiting GP was 4.8 days (compared to average 4.4 in other countries). Worth noting is that additional testing in diagnosis of RTIs was performed less frequently in Poland: rapid streptococcal test was conducted in 0.4% of cases (European average: 4.45%), CRP--in 2.2% of patients (average from other countries: 14.2%) and chest X-ray in 2.3% of cases compared to 14% in other project's participants. In Poland, the most frequently applied antibiotic was amoxicillin, which was used in 28.9% of cases ended with antibiotic prescribing (amoxicillin/pivampicillin were also predominant in other countries, excluding Sweden). In Poland, macrolides (22.4% of all prescriptions for antibiotic) and cephalosporins (12.1%) were frequently used. The results indicate that narrow-spectrum antibiotics are prescribed in Poland less frequently, with the example being penicillin V which was prescribed in 6.7% of patients with RTIs who were given antibiotic.
CONCLUSIONS
Comparing the results of Happy Audit 2 in Poland and other project's participants, the major differences consist in rare use of phenoxymethylpenicillin in favour of amoxicillin and macrolides as well as infrequent use of additional testing in diagnosis of RTIs in Poland.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Clinical Audit; Female; General Practitioners; Humans; Infant; Latvia; Lithuania; Male; Middle Aged; Poland; Practice Patterns, Physicians'; Primary Health Care; Respiratory Tract Infections; Russia; Sweden; Treatment Outcome; Young Adult
PubMed: 25004629
DOI: No ID Found -
Research in Veterinary Science Feb 2012Ampicillin concentrations in pulmonary epithelial lining fluid (PELF) and plasma was studied after single intravenous ampicillin administration (15mg/kg) or single... (Clinical Trial)
Clinical Trial
Ampicillin concentrations in pulmonary epithelial lining fluid (PELF) and plasma was studied after single intravenous ampicillin administration (15mg/kg) or single intragastric administration of its prodrug, pivampicillin (19.9mg/kg) to horses and discussed in relation to minimum inhibitory concentrations (MIC) of common equine respiratory pathogens. After intravenous administration, elimination of ampicillin was fast and not detectable in plasma after 12h in three out of six horses. Pivampicillin was absorbed well in non-fasted horses with an oral bioavailability of 36%. The degree of penetration of ampicillin into PELF, as described by the AUC(PELF)/AUC(plasma) ratio from 0 to 12h was 0.40 after intravenous administration and 1.00 after pivampicillin administration. In horses, ampicillin administered either intravenously or orally, in the form of pivampicillin, can provide clinically relevant drug concentrations in PELF for at least 12h, when treating susceptible equine respiratory pathogens (e.g. streptococci). Treatment of other bacterial pathogens requires susceptibility testing and possibly more frequent dosing, depending of minimum inhibitory concentrations (MIC) values.
Topics: Administration, Oral; Ampicillin; Animals; Anti-Bacterial Agents; Biological Availability; Bronchoalveolar Lavage Fluid; Chromatography, High Pressure Liquid; Female; Horses; Injections, Intravenous; Pivampicillin
PubMed: 21144541
DOI: 10.1016/j.rvsc.2010.11.001