Japanese spotted fever in an area endemic to SFTS virus: Case report and review of the literature.

RATIONALE: The geographic spread of Japanese spotted fever (JSF) in China is gradually expanding, particularly in regions where severe fever with thrombocytopenia syndrome (SFTS) is highly prevalent, with both diseases sharing similarities in epidemiology and clinical presentation. The microbiological diagnosis of JSF is challenging, compounded by low awareness among healthcare professionals in newly affected areas. Moreover, primary healthcare facilities without polymerase chain reaction (PCR) testing capabilities for SFTS often misdiagnose JSF as SFTS. PATIENT CONCERNS: All 3 patients had a history of working in the fields, with cold like symptoms in the early fever stages, but the fever did not improve after a few days. The accompanying symptoms were also very different. Physical examination revealed enlarged lymph nodes, different forms of rash, with or without eschar. Laboratory tests showed thrombocytopenia, eosinophilia, elevated lactate dehydrogenase, and transaminase, with 1 patient experiencing renal damage. It is worth noting that these 3 patients reside in an area where SFTS is endemic, and there have been no prior reports of JSF. They exhibited clinical symptoms and laboratory test results closely resembling those of SFTS. Therefore, they were initially misdiagnosed with SFTS in their local hospitals. DIAGNOSES: The 3 patients who arrived at our hospital 7 days after symptom onset and were subsequently diagnosed with JSF by metagenomic next-generation sequencing (mNGS). INTERVENTIONS: Doxycycline treatment for 1 week. OUTCOMES: The patients' symptoms quickly improved with no side effects, and the results of laboratory tests went back to normal. LESSONS: By comparing the clinical characteristics of JSF patients and SFTS patients comprehensively, we found that APTT and procalcitonin levels may be valuable in assisting in the identification of SFTS and JSF. In all areas where tick-borne diseases are endemic, include SFTS-epidemic areas, we recommend using the Weil-Felix test to screen for potential rickettsiosis in patients presenting with fever and thrombocytopenia with or without rash in primary healthcare settings, as well as simultaneous testing for the SFTS virus and spotted fever group rickettsioses sequence. Additionally, mNGS sequencing should be used to confirm the diagnosis and provide information for epidemiological investigations in patients who are suspected of having spotted fever group rickettsiosis.

Q fever endocarditis of the tricuspid valve transmitted in an urban setting with no livestock exposure: Case report.

BACKGROUND: Coxiella burnetii is a bacterium with extreme tenacity and contagiousness that is mainly transmitted by inhalation of contaminated aerosols. Nevertheless, a transmission by ticks is under discussion. We report a case of Q fever in an urban environment and far away from sheep breeding that caused a rare right-sided endocarditis. CASE PRESENTATION: A 55-year-old man who was in good health before the event developed a C. burnetii -endocarditis of the tricuspid valve. He had no contact with sheep and no recent travel in a rural or even endemic area. The infection originated in a strictly urban environment, and the patient's occupation as a cemetery gardener in Berlin, coupled with the close temporal and local exposure to wild boar, made a transmission by these animals a plausible hypothesis. The infection was confirmed by the German Reference Laboratory, and the patient recovered completely after treatment with doxycycline and hydrochlorquine. CONCLUSIONS: The specialities of this case report are the right-sided endocarditis and the transmission of C. burnetii in a metropolitan area without sheep contact. We think that this case should serve to increase awareness of the potential for Q fever infection even in non-rural areas.

[Do not overuse doxycycline as prophylaxis for uncomplicated sexually transmitted infections]. / Överanvänd inte doxycyklin som profylax mot STI.

STI prophylaxis using doxycycline is discussed internationally for persons at high risk of STIs (Doxy-PEP). Doxy-PEP would probably have limited effect on gonorrhoea due to resistance to tetracyclines. Doxy-PEP may reduce the incidence of chlamydia and syphilis, but would not reduce the number of complicated infections. Further studies are needed on the effects of intermittent antibiotic use on the microbiome or antibiotic resistance in general.

Systematic Identification of Kinase-Substrate Relationship by Integrated Phosphoproteome and Interactome Analysis.

The sensitivity of phosphorylation site identification by mass spectrometry (MS)-based phosphoproteomics has improved significantly. However, the lack of kinase-substrate relationship (KSR) data has hindered improvement of the range and accuracy of kinase activity prediction using phosphoproteome data. We herein describe the application of a systematic identification of KSR by integrated phosphoproteome and interactome analysis using doxycycline (Dox)-induced target kinase-overexpressing HEK-293 cells.

Epidemiological, clinical, biochemical, and treatment characteristics of brucellosis cases in Turkey.

INTRODUCTION: In our study, we aimed to evaluate the epidemiological features of brucellosis and the efficacy of different treatment options in patients with various organ involvements. METHODOLOGY: Patients diagnosed with brucellosis and treated in two different centers between 2009 and 2019 were retrospectively screened and evaluated regarding epidemiological and clinical features, laboratory findings, and treatment responses. RESULTS: The study included 297 complete-data patients (76% of rural patients were farmers). Farming (76%) and raw dairy (69%) were the main transmission methods. Most patients (98.6%) had positive tube agglutination tests. Ninety-two patients' blood and bodily fluid cultures grew Brucella spp. The incidence of leukopenia was 18.8%, thrombocytopenia 10.7%, anemia 34.3%, and pancytopenia 4.3%. Doxycycline and rifampicin were the major treatments, with streptomycin utilized in osteoarticular patients. Pregnant women with neurobrucellosis took ceftriaxone and trimethoprim-sulfamethoxazole. After one year, 7.1% of patients relapsed. Doxycycline + streptomycin and doxycycline + rifampicin had similar relapse rates (p = 0.799). The double- and triple-antibiotic groups had identical recurrence rates (p = 0.252). CONCLUSIONS: In uncomplicated brucellosis cases doxycycline + streptomycin and doxycycline + rifampicin treatments were equally effective. Again, there is no statistical difference in relapse development rates between double and triple combination treatments in uncomplicated brucellosis cases. Relapsed patients generally miss follow-ups, interrupt therapy, have osteoarticular involvement, and get short-term treatment. Patients with focused participation should be thoroughly checked at diagnosis and medicine, and treatment should be lengthy to prevent relapses.

Metagenomic next-generation sequencing assistance in identifying Mycobacterium iranicum pulmonary infection: A case report.

Nontuberculous mycobacteria (NTM) are important opportunistic pathogens in humans, mostly affecting the lungs, and potentially causing progressive disease in individuals with underlying diseases. The prevalence of NTM infections is increasing worldwide. However, Mycobacterium iranicum (M. iranicum) infections are less common. Here we report a 65-year-old female who developed pneumonia caused by Mycobacterium iranicum, which was detected in bronchoalveolar lavage fluid (BALF) through metagenomic next-generation sequencing (mNGS). The patient was treated with moxifloxacin, doxycycline, and sulfamethoxazole/trimethoprim. Symptoms were relieved and lung abnormalities were shown to be partially absorbed on the follow-up chest computed tomography (CT) scans. As we know, this is the first case of Mycobacterium iranicum pulmonary infection identified by mNGS in BALF.

Studies on Sorption and Release of Doxycycline Hydrochloride from Zwitterionic Microparticles with Carboxybetaine Moieties.

The aim of this study was to examine the use of zwitterionic microparticles as new and efficient macromolecular supports for the sorption of an antibiotic (doxycycline hydrochloride, DCH) from aqueous solution. The effect of relevant process parameters of sorption, like dosage of microparticles, pH value, contact time, the initial concentration of drug and temperature, was evaluated to obtain the optimal experimental conditions. The sorption kinetics were investigated using Lagergren, Ho, Elovich and Weber-Morris models, respectively. The sorption efficiency was characterized by applying the Langmuir, Freundlich and Dubinin-Radushkevich isotherm models. The calculated thermodynamic parameters (ΔH, ΔS and ΔG) show that the sorption of doxycycline hydrochloride onto zwitterionic microparticles is endothermic, spontaneous and favorable at higher temperatures. The maximum identified sorption capacity value is 157.860 mg/g at 308 K. The Higuchi, Korsmeyer-Peppas, Baker-Lonsdale and Kopcha models are used to describe the release studies. In vitro release studies show that the release mechanism of doxycycline hydrochloride from zwitterionic microparticles is predominantly anomalous or non-Fickian diffusion. This study could provide the opportunity to expand the use of these new zwitterionic structures in medicine and water purification.

Thymoquinone' potent impairment of multidrug-resistant Staphylococcus aureus NorA efflux pump activity.

The drug efflux pump is a crucial mechanism implicated in resistance to multiple antimicrobials. Thymoquinone (TQ) has evidently demonstrated multiple activities, antibacterial being the most effective. Knowledge about TQ activity against multidrug-resistant Staphylococcus aureus is very scarce. Therefore, the present study was conducted to investigate TQ resistance modulation in ciprofloxacin (CIP) and doxycycline (DO) multidrug-resistant S. aureus. Forty-seven samples were collected from different sources, and S. aureus was isolated and identified. Then, S. aureus resistance profiles to antimicrobials, N. sativa essential oil, and TQ; the correlation between TQ-MIC readings and disc diffusion; cartwheel and ethidium bromide (EtBr) accumulation assays; and norA gene expression were all described within silico molecular docking for TQ interactions with norA efflux pump protein. TQ-MICs ranged from 5-320 µg/ml. TQ down-regulated norA gene expression, resulting in a drop in efflux pump activity of 77.5-90.6% in the examined strains, comparable to that observed with verapamil. Exposure of S. aureus strains to CIP and DO raises the initial basal efflux pumping expression to 34.2 and 22.9 times, respectively. This induced efflux pumping overexpression was substantially reduced by 97.7% when TQ was combined with CIP or DO. There was a significant reduction of MICs of CIP and DO MICs by 2-15 and 2-4 folds, respectively, after treatment with 0.5XMIC-TQ in resistance modulation assays. These results refer to TQ ligand inhibitory interactions with NorA protein in molecular docking. Interpretations of inhibition zone diameters (IZDs) of disc diffusion and TQ-MICs exhibit independence of MICs from IZDs, as indicated by invalid linear regression analysis. TQ significantly reduced efflux pumping S. aureus induced by CIP and DO, but further investigations are needed to improve TQ-pharmacokinetics to restore CIP and DO activity and suppress fluoroquinolone and doxycycline-resistant S. aureus selection in clinical and animal settings.

Mycoplasma spp. pneumonia and subsequent pulmonary hypertension in a domestic ferret (Mustela putorius furo).

Treatment of Mycoplasma spp. pneumonia has rarely been described in domestic ferrets (Mustela putorius furo). A 10-month-old, 0.53 kg, female spayed domestic ferret was presented for oxygen-dependent, chronic dyspnea of one-month's duration. Physical examination findings included dyspnea, tachypnea, increased bronchovesicular sounds bilaterally, and an intermittent non-productive cough. Bloodwork abnormalities included a mild leukocytosis (8.6×103/µL), mild neutrophilia (4.0×103/µL), mild hypoalbuminemia (2.7 g/dL), mild hyperglobulinemia (3.3 g/dL), mild hyponatremia (147 mEq/L), and mild hypochloremia (111.4 mEq/L). Radiographs revealed a marked diffuse bronchial pattern with peribronchial cuffing, a mild main pulmonary artery bulge, distended caudal lobar pulmonary arteries, and decreased serosal detail within the abdomen. An echocardiogram revealed indications of moderate pulmonary hypertension and systolic anterior motion of the mitral valve. Polymerase chain reaction testing for Mycoplasma spp. was positive, and treatment was initiated with doxycycline (10 mg/kg PO q 12 h for 16 weeks), prednisolone (0.4 mg/kg PO q 12 h for 13 weeks, tapered to 0.2 mg/kg PO q 12 h for two weeks, then eventually increased to 0.7 mg/kg PO q 12 h until further notice), sildenafil (0.3 mg/kg PO q 24 h for 13 weeks), and oxygen supplementation via an oxygen cage for six weeks. On repeat echocardiogram eleven weeks after initiation of doxycycline therapy, the pulmonary hypertension had resolved. At follow up six months later, the ferret was stable on previously prescribed medications and did not require oxygen supplementation. Mycoplasma spp. and pulmonary hypertension should be considered in cases of respiratory distress in ferrets.

Doxycycline, a role in the treatment of onchocerciasis-associated epilepsy?

Can the antibiotic doxycycline unlock new possibilities in the fight against onchocerciasis-associated epilepsy (OAE)? Idro et al. explored this question by investigating for the first time doxycycline's impact on nodding syndrome (NS), a severe manifestation of OAE. Results reveal significant findings that may shape future treatment strategies.

Potential Crown Discoloration Induced by the Combination of Various Intracanal Medicaments and Scaffolds Applied in Regenerative Endodontic Therapy.

BACKGROUND: Regenerative endodontics involves the use of various root canal medicaments and scaffolds, which may cause crown discoloration. AIM: This study aimed to investigate the combined crown discoloration of scaffolds [platelet-rich fibrin (PRF) and blood clot] applied after administration of different medicaments [modified triple antibiotic paste including doxycycline (mTAPd), modified double antibiotic paste (mDAP), calcium hydroxide (CH), and propolis]. METHODS: In total, 100 human mandibular premolar teeth were selected and prepared. The teeth were apically resected to simulate immature teeth. The positive and negative control groups (n = 10) consisted solely of blood-only and serum-only samples. The remaining 80 teeth were used for the experimental groups with four different medicaments. Three weeks later, either blood or PRF was applied as a scaffold after removing the medicaments (n = 10). Color changes were assessed before medication placement and at the end of the first, second, and third weeks, as well as on days 0, 1, 30, 60, and 90 after scaffold application. Analysis was carried out using repeated measures of variance, Friedman, one-way ANOVA, Kruskal-Wallis, the dependent paired t-test, and Wilcoxon test. RESULTS: Statistical significance was determined at P = 0.05. All groups including blood and the group including propolis and PRF combination, resulted in a significant increase in discoloration (P < 0.05) and discoloration exceeding clinically acceptable thresholds. CONCLUSIONS: CH and the modified versions of TAP (mTAPd) and DAP (mDAP) demonstrated an acceptable level of discoloration when used with a combination of PRF at day 90.

Susceptibility of Neisseria gonorrhoeae against a dual treatment antibiotics regimen in primary health centres in Surabaya, Indonesia.

BACKGROUND AND OBJECTIVES: There were 82.4 million new gonorrhoea cases worldwide in 2020. Dual treatment with ceftriaxone or cefixime and azithromycin or doxycycline is currently recommended for gonorrhoea in Indonesia. However, reduced susceptibility and resistance to cephalosporins and azithromycin are increasing. We evaluated the susceptibility pattern of Neisseria gonorrhoeae to cefixime, ceftriaxone, azithromycin and doxycycline. METHOD: N. gonorrhoeae isolates were obtained from 19 male participants with clinically and laboratory-confirmed gonorrhoea. Antibiotic susceptibility testing was conducted by disc diffusion and interpreted according to Clinical and Laboratory Standards Institute and Centers for Disease Control and Prevention criteria. RESULTS: Reduced susceptibility or resistance was observed against doxycycline in 19 isolates (100%), cefixime in six (31.6%), ceftriaxone in three (15.8%) and azithromycin in zero (0%) isolates. DISCUSSION: A dual treatment regimen with ceftriaxone and azithromycin can still be recommended as first-line therapy for gonorrhoea in Indonesia. Antibiotic susceptibility surveillance of N. gonorrhoeae should be routinely conducted.

Acute intravascular haemolysis associated with scrub typhus.

Scrub typhus, a prevalent tropical infection, may sometimes manifest with unusual complications. Here, we present the case of a young man who was admitted to our facility with a fever for the past 3 days and passage of dark-coloured urine since that morning. On investigation, we identified intravascular haemolytic anaemia. Through meticulous examination, a black necrotic lesion (eschar) was discovered on his right buttock, a pathognomonic sign of scrub typhus infection. Treatment was initiated with oral doxycycline 100 mg two times a day. Subsequently, diagnosis of scrub typhus was confirmed through positive results from scrub typhus IgM via ELISA and PCR analysis from the eschar tissue. The patient responded well to oral doxycycline and his symptoms resolved within the next few days. This case highlights severe intravascular haemolysis associated with scrub typhus infection.

A novel microfluidic tool for the evaluation of local drug delivery systems in simulated in vivo conditions.

A 3D-printed microfluidic tool for assessing local drug delivery systems (LDD) in simulated in vivo conditions was developed and evaluated. The device was designed considering the oral environment and dental applications, and it was fabricated with a high-precision resin 3D printer. Chitosan scaffolds loaded with different concentrations of doxycycline were used for evaluating our device. The concentration of the released drug was measured through in-line UV-VIS spectroscopy, and to verify the repeatability and accuracy of our measurements, comparisons with standard HPLC results were made (5% deviation). Cumulative drug release profiles in steady-state conditions were obtained and compared to the Weibull model. The behaviour of the LDD system in a dynamic environment was also evaluated during experiments where step changes in pH were introduced. It was demonstrated that under infection-like conditions, there is an immediate response from the polymer and a clear increase in the concentration of the released drug. Continuous flow and recirculation experiments were also conducted, revealing significant differences in the drug release profiles. Specifically, in the case of continuous flow, the quantity of the released drug is much higher due to the higher driving force for diffusion (concentration gradient). Overall, the proposed microfluidic tool proved to be ideal for evaluating LDD systems, as the in vivo microenvironment can be replicated in a better way than with currently used standard systems.

Design, Synthesis, and Evaluation of a Novel Conjugate Molecule with Dopaminergic and Neuroprotective Activities for Parkinson's Disease.

The escalating prevalence of Parkinson's disease (PD) underscores the need for innovative therapeutic interventions since current palliative measures, including the standard l-Dopa formulations, face challenges of tolerance and side effects while failing to address the underlying neurodegenerative processes. Here, we introduce DAD9, a novel conjugate molecule that aims to combine symptomatic relief with disease-modifying strategies for PD. Crafted through knowledge-guided chemistry, the molecule combines a nonantibiotic doxycycline derivative with dopamine, preserving neuroprotective attributes while maintaining dopaminergic agonism. This compound exhibited no off-target effects on PD-relevant cell functions and sustained antioxidant and anti-inflammatory properties of the tetracycline precursor. Furthermore, it effectively interfered with the formation and seeding of toxic α-synuclein aggregates without producing detrimental oxidative species. In addition, DAD9 was able to activate dopamine receptors, and docking simulations shed light onto the molecular details of this interaction. These findings position DAD9 as a potential neuroprotective dopaminergic agonist, promising advancements in PD therapeutics.

Strain-level variations of Dirofilaria immitis microfilariae in two biochemical assays.

BACKGROUND: The increase in reports of resistance to macrocyclic lactones in the canine heartworm, Dirofilaria immitis is alarming. While DNA based tests have been well-validated, they can be expensive. In a previous study, we showed that two biochemical tests adapted to a 96- well plate format and read in a spectrophotometer could detect differences among lab validated D. immitis isolates. The two tests- Resazurin reduction and Hoechst 33342 efflux-detect metabolism and P-glycoprotein activity respectively in microfilariae isolated from infected dog blood. METHODS: Our objective was to optimize the two assays further by testing various assay parameters in D. immitis isolates not tested previously. We tested microfilarial seeding density, incubation time and the effect of in vitro treatment with ivermectin and doxycycline in five other D. immitis isolates-JYD-34, Big Head, Berkeley, Georgia III and LOL. All assays were performed in 3 technical replicates and 2-4 biological replicates. To understand the molecular basis of the assays, we also performed qPCR for selected drug metabolism and elimination associated genes of the ABC transporter and cytochrome P450 gene families. RESULTS: Metabolism and ABC transporter activity as detected by these assays varied between strains. Anthelmintic status (resistant or susceptible) did not correlate with metabolism or P-gp efflux. Basal transcriptional variations were found between strains in ABC transporter and cytochrome P450 genes. CONCLUSIONS: These assays provide a greater understanding of the biochemical variation among isolates of D. immitis, which can be exploited in the future to develop in vitro diagnostic tests capable of differentiating susceptible and resistant isolates.

Lymphogranuloma venereum of the neck in a young man living with HIV: a rare extragenital presentation.

Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by an invasive form of Chlamydia trachomatis, typically affecting the anogenital area with regional lymphatic involvement. Extragenital manifestations are rare but can occur, particularly if the bacterium is inoculated out of the genital tract. To our knowledge, only 13 cases of symptomatic neck LGV have been published so far in the medical literature. We describe a case of a young man living with HIV with bilateral, rapid-growing and painful neck swelling, whose definite diagnosis was challenging. The patient underwent extensive investigation, including repeated ultrasound-guided fine-needle aspirations, microbiological exams and histological characterisation. Genotyping revealed C. trachomatis L2 serovar, confirming LGV as a final diagnosis, affecting neck lymph nodes. Treatment with doxycycline combined with surgical drainage led to clinical resolution. This case emphasises the importance of a comprehensive testing strategy to identify LGV, especially in individuals reporting unprotected oral sex, with unexplained neck lymphadenitis.

Dirofilariasis presenting as pleural effusion: a rare case report with unusual manifestations and treatment modalities.

BACKGROUND: We present an extremely rare manifestation of dirofilariasis in the pleural cavity. This is the first human pulmonary dirofilariasis reported in Lithuania; according to our knowledge, only two other patients were documented with this pathology in the world. CASE PRESENTATION: A 72-year-old woman was admitted to the hospital complaining of dyspnea, left-side chest pain, and a dry cough. She was a retiree living alone in the countryside without domestic pets (sometimes stray dogs appear) or a travel history. A complete blood count was within normal limits, with a CRP level of 16.8 mg/l and D-dimer concentration of 900 µg/l, which raised suspicion of pulmonary embolism. In chest computed tomography angiography, pulmonary embolism was excluded, and only left pleural effusion without abnormal lesions was confirmed. Left thoracocentesis was performed, and the pleural fluid was evaluated as an exudate with a predominance of eosinophils (59%), along with the presence of parasites. These parasites exhibited the morphology of Dirofilaria repens. Oral doxycycline (100 mg, twice daily) and albendazole (400 mg, twice daily) were prescribed for a 14-day course. A month later, there were no pathological findings on the chest X-ray, and the patient no longer had respiratory symptoms. However, the patient presented with an emerged, painful palpable right breastmass, where the rash was previously observed. Ultrasound imaging revealed a 1.5 × 2 cm nodule, which was surgically removed. Parasites consistent with Dirofilaria repens were suspected but not definitively identified. Pharmacological treatment for dirofilariasis was not further prescribed. CONCLUSIONS: This case encourages doctors to be more vigilant because the patient, who neither travelled nor kept any pets, contracted dirofilariasis. Diagnostic and treatment guidelines are lacking, necessitating further research. Treatment with doxycycline and albendazole yielded positive outcomes, suggesting potential efficacy for dirofilarial pleuritis.

Construction of colorimetric sensor arrays using steel slag-based composites for highly sensitive detection of tetracycline antibiotics.

Sensor array methods have received much attention in recent years. In this study, a colorimetric sensor array consisting of three kinds of steel slag-based composites (including porphyrin-functionalized non-magnetic steel slag (NMSS-Por), alkali-excited steel slag (A-SS), and platinum modified steel slag (ALANH-Pt)) was developed for the detection and recognition of tetracycline antibiotics (TCs) such as tetracycline (TC), oxytetracycline (OTC) and doxycycline (DOX). Linear discriminant analysis (LDA) and hierarchical cluster analysis (HCA) showed that the colorimetric sensor array has excellent recognition ability for TCs. The detection limits of this sensor array for TC, OTC, and DOX were 0.059 µM, 0.111 µM and 0.118 µM, respectively, which provided higher sensitivity compared to the colorimetric sensors composed of a single steel slag-based composite material. At the same time, the array sensor has anti-interference ability, and this study provides a new application route for steel slag.