Cat-scratch disease: a rare cause of osteomyelitis.

Cat-scratch disease is a zoonosis caused by Bartonella henselae, characterised by regional lymphadenopathy. Rarer presentations, such as osteomyelitis, can occur.We present an adolescent girl with severe right lumbar pain and fever, without animal contacts or recent travels. On examination, pain on flexion of torso, movement limitation and marked lordosis were noted, but there were no inflammatory signs, palpable masses or lymph nodes. Serological investigations revealed elevated inflammatory markers. Imaging revealed a paravertebral abscess with bone erosion. Several microbiological agents were ruled out. After a second CT-guided biopsy, PCR for Bartonella spp was positive. At this point, the family recalled having a young cat some time before. Cat-scratch disease was diagnosed, and complete recovery achieved after treatment with doxycycline and rifampicin.Cat-scratch disease is a challenging diagnosis in the absence of typical features. However, B. henselae must be investigated if common pathogens are ruled out and response to therapy is poor.

Doxycycline protects against sepsis-induced endothelial glycocalyx shedding.

Endothelial glycocalyx (eGC) covers the inner surface of the vessels and plays a role in vascular homeostasis. Syndecan is considered the "backbone" of this structure. Several studies have shown eGC shedding in sepsis and its involvement in organ dysfunction. Matrix metalloproteinases (MMP) contribute to eGC shedding through their ability for syndecan-1 cleavage. This study aimed to investigate if doxycycline, a potent MMP inhibitor, could protect against eGC shedding in lipopolysaccharide (LPS)-induced sepsis and if it could interrupt the vascular hyperpermeability, neutrophil transmigration, and microvascular impairment. Rats that received pretreatment with doxycycline before LPS displayed ultrastructural preservation of the eGC observed using transmission electronic microscopy of the lung and heart. In addition, these animals exhibited lower serum syndecan-1 levels, a biomarker of eGC injury, and lower perfused boundary region (PBR) in the mesenteric video capillaroscopy, which is inversely related to the eGC thickness compared with rats that only received LPS. Furthermore, this study revealed that doxycycline decreased sepsis-related vascular hyperpermeability in the lung and heart, reduced neutrophil transmigration in the peritoneal lavage and inside the lungs, and improved some microvascular parameters. These findings suggest that doxycycline protects against LPS-induced eGC shedding, and it could reduce vascular hyperpermeability, neutrophils transmigration, and microvascular impairment.

Doxycycline inhibits neurotropic enterovirus proliferation in vitro.

Human enteroviruses (EVs) represent a global public health concern due to their association with a range of serious pediatric illnesses. Despite the high morbidity and mortality exerted by EVs, no broad-spectrum antivirals are currently available. Herein, we presented evidence that doxycycline can inhibit in vitro replication of various neurotropic EVs, including enterovirus A71 (EV-A71), enterovirus D68 (EV-D68), and coxsackievirus (CV)-A6, in a dose-dependent manner. Further investigations indicated that the drug primarily acted at the post-entry stage of virus infection in vitro, with inhibitory effects reaching up to 89 % for EV-A71 when administered two hours post-infection. These findings provide valuable insights for the development of antiviral drugs against EV infections.

The impact of socio-environmental factors on doxycycline post-exposure prophylaxis awareness in the US: a cross-sectional study.

Background We investigated awareness and use of doxycycline post-exposure prophylaxis (doxyPEP) in the US. DoxyPEP has preventative benefits for bacterial STIs among people assigned male at birth. We considered how individual, interpersonal and social determinants of health, such as state-level LGBTQ equality, impact doxyPEP awareness. Methods We conducted an online snapshot cross-sectional survey in June 2023. Survey questions included demographics, sexual and substance use behaviours, and socio-environmental factors, and provided a short explanation of doxyPEP, with questions regarding prior awareness and use. Results Among a racially diverse sample of 196 participants (median age 33 years), 94% identified as cisgender men, 26% were aware of doxyPEP, whereas only 14 (7%) had ever used it. Factors significantly associated with awareness included being college educated (OR 2.50, 95% CI 1.09-5.74), a past year bacterial STI (OR 4.20, 95% CI 1.97-8.89), having discussed HIV pre-exposure prophylaxis with a health care provider (OR 3.88, 95% CI 1.99-7.57) and having taken HIV pre-exposure prophylaxis (OR 2.29, 95% CI 1.11-4.70). Socio-environmental factors associated with doxyPEP awareness included living in a large urban city (OR 2.14, 95% CI 1.12-4.10) and living in a state with higher levels of LGBTQ policy equality (OR 2.18, 95% CI 1.07-4.44). Conclusions Considering the disproportionate impact of bacterial STIs on men who have sex with men, especially those living in lower LGBTQ equality regions, such as the Southern US, our study emphasises how socio-environmental factors may limit awareness and uptake of novel biomedical approaches that have the potential to prevent morbidity and enhance sexual health.

The case of Mediterranean spotted fever of the traveler returned from Zambia.

We report the case of a traveler who returned from Zambia and was diagnosed with Mediterranean spotted fever (MSF), an infectious disease caused by Rickettsia conorii conorii. The patient presented to Sapporo City General Hospital with symptoms of fever, malaise, headache, and rash. The pathogen was identified by Polymerase Chain Reaction assays and subsequent analyses. The patient improved with 10-day treatment of oral doxycycline. Although some cases of MSF have been reported in sub-Saharan Africa, none have been reported in Zambia. Rhipicephalus sanguineus sensu lato, the vector of the Rickettsia conorii conorii, has been found in various areas of Zambia. Our case report highlights the potential threat of Mediterranean spotted fever in urban areas of Zambia.

Controlled cell proliferation and immortalization of human dental pulp stem cells with a doxycycline-inducible expression system.

Human dental pulp stem cells are a potentially useful resource for cell-based therapies and tissue repair in dental and medical applications. However, the primary culture of isolated dental pulp stem cells has notably been limited. A major requirement of an ideal human dental pulp stem cell culture system is the preservation of efficient proliferation and innate stemness over prolonged passaging, while also ensuring ease of handling through standard, user-friendly culture methods. In this study, we have engineered a novel human dental pulp stem cell line, distinguished by the constitutive expression of telomerase reverse transcriptase (TERT), and the conditional expression of the R24C mutant cyclin-dependent kinase 4 (CDK4R24C) and Cyclin D1. We have named this cell line Tet-off K4DT hDPSCs. Furthermore, we have conducted a comprehensive comparative analysis of their biological attributes in relation to a previously immortalized human dental pulp stem cells, hDPSC-K4DT, which were immortalized by the constitutive expression of CDK4R24C, Cyclin D1 and TERT. In Tet-off K4DT cells, the expression of the K4D genes can be precisely suppressed by the inclusion of doxycycline. Remarkably, Tet-off K4DT cells demonstrated an extended cellular lifespan, increased proliferative capacity, and enhanced osteogenic differentiation potential when compared to K4DT cells. Moreover, Tet-off K4DT cells had no observable genomic aberrations and also displayed a sustained expression of stem cell markers even at relatively advanced passages. Taken together, the establishment of this new cell line holds immense promise as powerful experimental tool for both fundamental and applied research involving dental pulp stem cells.

Perceptions about doxycycline post-exposure prophylaxis (Doxy-PEP) as an STI-prevention strategy among gay and bisexual men (GBM) in the United States: Results from a qualitative study.

OBJECTIVE: To leverage qualitative data to explore gay and bisexual men's (GBM) perceptions about doxycycline post-exposure prophylaxis (Doxy-PEP). Doxy-PEP is a novel biomedical STI-prevention strategy that helps reduce the risk of acquiring bacterial STIs. Little is known about Doxy-PEP's acceptability in the U.S., nor how best to engage those most vulnerable to STIs in taking up this nascent prevention strategy. METHOD: Between July and September of 2023, 24 GBM from across the U.S. completed qualitative interviews about their perceptions regarding Doxy-PEP. Interviews were analyzed using a codebook approach to thematic analysis. RESULTS: Participants were generally interested in using Doxy-PEP, but were concerned about the potential for antibiotic resistance, side-effects, medication interactions to occur, along with stigmatizing discourse around its use. Meanwhile, participants were motivated by the simplicity of Doxy-PEP and the protection it could confer on both an individual and community-level- as well as its potential to reduce STI-related anxiety. Finally, participants desired additional information on Doxy-PEP to address their concerns. CONCLUSIONS: There is a need for clear guidelines and expanded public health messaging on Doxy-PEP in the U.S.

mNGS helped diagnose scrub typhus-associated HLH in children: a report of two cases.

Background: Scrub typhus, caused by the Orientia tsutsugamushi (Ot), is a widespread vector-borne disease transmitted by chigger mites. Hemophagocytic lymphohistiocytosis (HLH) is considered to be one of the potentially severe complications. The diagnosis of scrub typhus-associated HLH may be overlooked due to the non-specific clinical characteristics and the absence of pathognomonic eschar. Case presentation: We obtained clinical data from two patients in the South of Sichuan, China. The first case involved a 6-year-old girl who exhibited an unexplained fever and was initially diagnosed with sepsis, HLH, and pulmonary infection. The other patient presented a more severe condition characterized by multiple organ dysfunction and was initially diagnosed with septic shock, sepsis, HLH, acute kidney injury (AKI), and pulmonary infection. At first, a specific examination for scrub typhus was not performed due to the absence of a characteristic eschar. Conventional peripheral blood cultures yielded negative results in both patients, and neither of them responded to routine antibiotics. Fortunately, the causative pathogen Orientia tsutsugamushi (Ot) was detected in the plasma samples of both patients using metagenomics next-generation sequencing (mNGS) and further confirmed by polymerase chain reaction. Subsequently, they both were treated with doxycycline and recovered quickly. Conclusion: The unbiased mNGS provided a clinically actionable diagnosis for an uncommon pathogen-associated infectious disease that had previously evaded conventional diagnostic approaches.

Inhibitory effect of doxycycline conjugated with deoxycholic acid and polyethylenimine conjugate on nasal fibroblast differentiation and extracellular production.

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disease affecting the sinuses or nose. Persistent inflammatory responses can lead to tissue remodeling, which is a pathological characteristics of CRS. Activation of fibroblasts in the nasal mucosal stroma, differentiation and collagen deposition, and subepithelial fibrosis have been associated with CRS. OBJECTIVES: We aimed to assess the inhibitory effects of doxycycline and deoxycholic acid-polyethyleneimine conjugate (DA3-Doxy) on myofibroblast differentiation and extracellular matrix (ECM) production in nasal fibroblasts stimulated with TGF-ß1. METHODS: To enhance efficacy, we prepared DA3-Doxy using a conjugate of low-molecular-weight polyethyleneimine (PEI) (MW 1800) and deoxycholic acid (DA) and Doxy. The synthesis of the DA3-Doxy polymer was confirmed using nuclear magnetic resonance, and the critical micelle concentration required for cationic micelle formation through self-assembly was determined. Subsequently, the Doxy loading efficiency of DA3 was assessed. The cytotoxicity of Doxy, DA3, PEI, and DA-Doxy in nasal fibroblasts was evaluated using the WST-1 assay. The anti-tissue remodeling and anti-inflammatory effects of DA3-Doxy and DA3 were examined using real-time polymerase chain reaction (Real-time PCR), immunocytochemistry, western blot, and Sircol assay. RESULTS: Both DA3 and DA3-Doxy exhibited cytotoxicity at 10 µg/ml in nasal fibroblasts. Doxy partially inhibited α-smooth muscle actin, collagen types I and III, and fibronectin. However, DA3-Doxy significantly inhibited α-SMA, collagen types I and III, and fibronectin at 5 µg/ml. DA3-Doxy also modulated TGF-ß1-induced changes in the expression of MMP 1, 2, and 9. Nonetheless, TGF-ß1-induced expression of MMP3 was further increased by DA3-Doxy. The expression of TIMP 1 and 2 was partially reduced with 5 µg/ml DA3-Doxy. CONCLUSIONS: Although initially developed for the delivery of genetic materials or drugs, DA3 exhibits inhibitory effects on myofibroblast differentiation and ECM production. Therefore, it holds therapeutic potential for CRS, and a synergistic effect can be expected when loaded with CRS treatment drugs.

Treatment of peri-implantitis using nonsurgical debridement combined with bioresorbable doxycycline nanospheres: a case report with 3-year follow-up.

Treatment of peri-implant diseases focuses on reducing the bacterial load and consequent infection control. The use of local antimicrobials as an adjunct to mechanical therapy may result in a better outcome. Among antimicrobials, doxycycline stands out because of its local modulation of cytokines, microbial reduction, and clinical parameters in the treatment of periodontal diseases. The objective of this case report was to describe the combined application of mechanical debridement and bioresorbable doxycycline-loaded nanospheres for the treatment of peri-implantitis in a 71-year-old man. At the 3-year evaluation, the peri-implant tissues had improved, showing decreased probing depths, an absence of bleeding on probing, and no suppuration. This case report highlights the importance of supportive therapy, which is essential for the long-term success of peri-implantitis treatment.

Molecular imprinting-based triple-emission ratiometric fluorescence sensor with aggregation-induced emission effect for visual detection of doxycycline.

The development of high-performance sensors for doxycycline (DOX) detection is necessary because its residue accumulation will cause serious harm to human health and the environment. Here, a novel tri-emission ratiometric fluorescence sensor was proposed by using "post-mixing" strategy of different emissions fluorescence molecularly imprinted polymers with salicylamide as dummy template (DMIPs). BSA was chosen as assistant functional monomer, and also acted as sensitizers for the aggregation-induced emission (AIE) effect of DOX. The blue-emitting carbon dots and the red-emitting CdTe quantum dots were separately introduced into DMIPs as the response signals. Upon DOX recognition within 2 min, blue and red fluorescence of the tri-emission DMIPs sensor were quenched while green fluorescence of DOX was enhanced, resulting in a wide range of color variations observed over bluish violet-rosered-light pink-orange-yellow-green with a detection limit of 0.061 µM. The sensor possessed highly selective recognition and was successfully applied to detect DOX in complicated real samples. Moreover, with the fluorescent color collection and data processing, the smartphone-assisted visual detection of the sensors showed satisfied sensitivity with low detection limit. This work provides great potential applications for rapid and visual detection of antibiotics in complex substrates.

A case report of Vancomycin in the treatment of Q fever endocarditis.

The patient, a 43-year-old male, was admitted to the hospital with gradually aggravated exertional palpitations and chest tightness over a 2-day period. Upon hospital admission, a cardiac ultrasound revealed aortic valve redundancy, however multiple blood culture investigations came back negative. Blood mNGS was perfected, revealing Coxiella burnetii, and the diagnosis of Q fever (query fever) was established. The temperature and inflammatory indices of the patient were all normal with the treatment of vancomycin before cardiac surgery. But for the potential liver damage of and the Coxiella burnetii was still positive in the anti-phase II IgG titer, the doxycycline and hydroxychloroquine instead of vancomycin were applied for the patient. Despite receiving standardized anti-infective therapy of doxycycline combined with hydroxychloroquine, this patient had fever and increased leukocytes following surgery. After the addition of vancomycin as an anti-infective treatment, the temperature and leukocytes improved quickly. During the treatment of vancomycin, a discovery of liver injury may have resulted. These findings provide new therapy options for future professionals.

Extended blood stage sensitivity profiles of Plasmodium cynomolgi to doxycycline and tafenoquine, as a model for Plasmodium vivax.

Testing Plasmodium vivax antimicrobial sensitivity is limited to ex vivo schizont maturation assays, which preclude determining the IC50s of delayed action antimalarials such as doxycycline. Using Plasmodium cynomolgi as a model for P. vivax, we determined the physiologically significant delayed death effect induced by doxycycline [IC50(96 h), 1,401 ± 607 nM]. As expected, IC50(96 h) to chloroquine (20.4 nM), piperaquine (12.6 µM), and tafenoquine (1,424 nM) were not affected by extended exposure.

Efficacy of antibiotic prophylaxis to preventing brucellosis in accidental exposure: A systematic review.

BACKGROUND: Antibiotic prophylaxis to prevent brucellosis after accidental exposure to Brucella is an important topic in public health. This study aimed to systematically review the efficacy of antibiotic prophylaxis following accidental exposure to Brucella in preventing human brucellosis disease. METHODS: The study protocol was registered in PROSPERO (CRD42023456812). The outcomes included the incidence of brucellosis disease, adverse events rate, and antibiotic prophylaxis adherence. A comprehensive literature search, conducted until 20 November, 2023, involved Medline, Embase, Cochrane Library, and LILACS databases. Descriptive analysis and meta-analysis using R software were performed, risk of bias was assessed using JBI Critical appraisal tools, and certainty of evidence was assessed using the GRADE tool. RESULTS: Among 3102 initially identified records, eight studies involving 97 individuals accidentally exposed, all focused on high-risk accidental exposure to Brucella in laboratory settings, were included in the review. All studies reported the prophylactic treatment comprising doxycycline at a dosage of 100 mg twice daily, combined with rifampicin at 600 mg, both administered over 21 days. Prophylaxis adherence was reported in 86% of cases, and incidence of brucellosis post-treatment was 0.01. Adverse events, mainly gastrointestinal, occurred in 26% of cases. Critical appraisal revealed limitations in reporting demographics and clinical information. The certainty of evidence was rated as 'very low,' emphasising the need for caution in interpreting the observed outcomes due to study design constraints and the absence of comparative groups. CONCLUSIONS: PEP is an alternative practice reported in the literature, used in accidents with high-risk exposure to Brucella. The currently available evidence of the efficacy of antibiotic prophylaxis is insufficient to support a recommendation for or against the widespread use of antibiotic prophylaxis, so caution is needed in interpreting results due to the very low certainty of evidence, primarily stemming from case series and lack of comparative groups.