Pyoderma gangrenosum (PG) is a chronic inflammatory neutrophilic dermatosis often presenting as a solitary enlarging painful ulcer with red to violaceous undermined borders. This report delves into the role of doxycycline in the treatment of PG in a 44-year-old male COVID-19 positive patient who has concomitant active tuberculosis infection and end-stage kidney disease, for which both first-line treatments (systemic corticosteroid and cyclosporine) are contraindicated. After three months on doxycycline and topical corticosteroids, there was resolution of the ulcers and no note of recurrence up to three months from completion of the treatment regimen.

OBJECTIVE: To investigate the mechanism of the in vitro toxicity of doxycycline to myeloma cell line H929 and also the possible pathway involved its toxicity. METHODS: Myeloma cell line H929 was treated with DOX, MEK inhibitor U0126 or RAS agonist ML-098, either alone or in combination. Then, the expression of p-MEK, caspase-3, caspase-9 and c-Jun in H929 were used to detected by Western blot; the cells proliferation and apoptosis were detected by CCK-8 assay and flow cytometry, respectively. RESULTS: DOX significantly increased the levels of cleaved caspase-3 and caspase-9, and down-regulated the level of p-MEK in H929 (P<0.05). MEK antagonist U0126 significantly increased the levels of cleaved caspase-3 and caspase-9, and down-regulated the level of p-MEK (P<0.05). After Dox combined with ML-098 treatment of H929 cells, the apoptosis rate of H929 cells was lower than that of DOX alone treatment group(P<0.05). Compared with DOX alone treatment group, the expressions of p-MEK and p-ERK1/2 in DOX+ML-098 combined treatment group were increased, and the levels of cleaved caspase-3,9 in H929 cells were decreased (P<0.05). The levels of c-Jun mRNA and protein increased in H929 when treated by DOX alone (P<0.05). CONCLUSION DOX can induce apoptosis of H929 via intrinsic apoptosis pathway, and MEK/ERK pathway and c-Jun possibly play a role in this process.
Apoptosis ; Caspase 3 ; Caspase 9/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Doxycycline/pharmacology* ; Humans ; Mitogen-Activated Protein Kinase Kinases/pharmacology* ; Multiple Myeloma

OBJECTIVE: To investigate the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in multiple myeloma (MM) patients, and analyze the effect of doxycycline (DOX) on the expression of MMP-2 and MMP-9 in MM cells. METHODS: The peripheral blood and bone marrow samples of MM patients were collected, and the patients were divided into three groups: newly diagnosed group, remission group and relapsed/refractory group, while the peripheral blood samples of 34 health people and the bone marrow samples of 17 IDA patients were selected as normal control and control group. The levels of MMP-2 and MMP-9 were detected by ELISA. The protein levels of MMP-2 and MMP-9 in H929 cells treated by different concentrations of DOX were analyzed by Western blot. After H929 cells was treated by Akt inhibitor MK-2206 2HCl in combination with DOX, Western blot was used to detect the levels of MMP-2 and MMP-9. RESULTS: The levels of MMP-2 and MMP-9 in newly diagnosed MM patients were higher than those in control (P<0.05), while for the patients in the remission group were decreased, but still higher than those in control. The levels of MMP-2 and MMP-9 were increased again for the patients in relapsed/refractory group, and showed no significant difference as compared with those in newly diagnosed group. The levels of MMP-2 and MMP-9 could be inhibited by 10 mg/L and 15 mg/L DOX treated by H929 cell. The protein levels of MMP-2 and MMP-9 showed no altered in H929 cells treated by 5 nmol/L MK-2206 2HCl alone. DOX exerted more profound inhibitory effect to MMP-2 and MMP-9 expression in H929 cells when Akt inhibitor MK-2206 2HCl was combined with DOX. CONCLUSION The levels of MMP-2 and MMP-9 are increased in MM patients and related to the disease status of MM. DOX can inhibit the expression of MMP-2 and MMP-9 in MM cells, and antagonizing its activation of Akt signaling pathway can further enhance the inhibitory effect.
Doxycycline/pharmacology* ; Humans ; Matrix Metalloproteinase 2/metabolism* ; Matrix Metalloproteinase 9/metabolism* ; Multiple Myeloma/metabolism* ; Proto-Oncogene Proteins c-akt

Background: Acne vulgaris is a common chronic inflammatory skin disease. Long term therapy involving antibiotics warrants for drug with a long half-life to increase compliance of patients. Methods: A twelve-week prospective randomized study was performed on 40 subjects with moderate to severe facial acne to compare the efficacy of oral azithromycin with oral doxycycline. Thirty-six subjects completed the study. Subjects in azithromycin group received azithromycin 250mg three times a week plus topical benzoyl peroxide 5% (BPO), whereas subjects in doxycycline group received doxycycline 100mg daily plus topical BPO 5%. Efficacy evaluation included treatment success rate (Comprehensive Acne Severity Score /CASS of 0 or 1 or improvement of two grades from baseline) and lesion counts. Results: Treatment was successful in 94.4% of subjects in azithromycin group, compared to 88.9% in doxycycline group (p=1.000) at week 12.However, percentage of clear or almost clear by CASS was higher in the doxycycline group ( 83.3% vs 66.7%; p= 0.443).Percentage reduction of inflammatory lesion counts in azithromycin and doxycycline group following treatment for 12 weeks were 78.3% and 85.3% (p=0.133) respectively, whereas for non-inflammatory lesion counts were 77.7% and 78.8% (p=0.852) respectively. Nausea was reported in 77.8% at week 6 and 66.7% at week 12 in doxycycline group, but none in azithromycin group. There were no significant differences in incidence of diarrhoea and abdominal pain. Conclusion Azithromycin 250mg three times a week plus topical BPO 5% is as effective as doxycycline 100mg daily plus topical BPO 5%.
Azithromycin ; Doxycycline ; Acne Vulgaris--therapy

PURPOSE: To report polymicrobial keratitis involving Pseudomonas aeruginosa, Acinetobacter baumannii, and Ochrobactrum anthropi. CASE SUMMARY: A 53-year-old female complained of pain and secretion in her right eye, which started 6 weeks before her visit. She applied steroid ointment, which was received from the dermatologist, to her eyelid 7 days prior to her visit but this treatment worsened her symptoms. At the initial visit, the visual acuity of the right eye was light perception, and purulent secretions were observed. Using a slit lamp, severe conjunctival hyperemia, hypopyon, and a ring-shaped central corneal ulcer were observed. The anterior chamber and fundus were not observed due to corneal lesions but ultrasonography showed no intraocular inflammation. Infectious keratitis was suspected and cultured by corneal scraping. During the incubation period, 0.5% moxifloxacin, 2% voriconazole, and 1% cyclopentolate were administered. A total of 400 mg of moxifloxacin and 100 mg of doxycycline were given orally. In the primary culture, Pseudomonas aeruginosa and Acinetobacter baumannii were identified so 5% ceftazidime, which was sensitive for the antibiotic susceptibility results was further instilled. Thereafter, the keratitis improved but the keratitis again worsened while maintaining the topical treatment. A secondary culture was positive for Ochrobactrum anthropi. Treatment with 1.4% gentamicin, which was sensitive for the antibiotic susceptibility test was added and the keratitis improved. A conjunctival flap was performed because of the increased risk of perforation. CONCLUSIONS: We report polymicrobial keratitis involving Pseudomonas aeruginosa, Acinetobacter baumannii, and Ochrobactrum anthropi for the first time in the Republic of Korea.
Acinetobacter baumannii ; Acinetobacter ; Anterior Chamber ; Ceftazidime ; Corneal Ulcer ; Cyclopentolate ; Doxycycline ; Eyelids ; Female ; Gentamicins ; Humans ; Hyperemia ; Inflammation ; Keratitis ; Middle Aged ; Ochrobactrum anthropi ; Ochrobactrum ; Pseudomonas aeruginosa ; Pseudomonas ; Republic of Korea ; Slit Lamp ; Ultrasonography ; Visual Acuity ; Voriconazole

OBJECTIVE: To assess positive culture rate and antimicrobial susceptibilities of Mycoplasma hominis (MH) and Ureaplasma urealyticum (UU) in symptomatic general population and pregnant women admitted with preterm labor and premature rupture of membranes. METHODS: We retrospectively reviewed medical records of patients who have undergone culture test and antimicrobial susceptibilities at our center from January 2017 to April 2018. Patients with positive culture for MH, UU, or both were included in this study. RESULTS: There were 200 patients who were eligible for enrollment. Of these patients, 34 (17%) were pregnant women and 166 (83%) were non-pregnant women. Of these 200 patients, positive culture results were as follows: MH only, n=10 (5%); UU only, n=58 (29%); and both MH and UU, n=36 (18%). Susceptibilities of MH only to doxycycline, erythromycin, ciprofloxacin, and azithromycin were 100%, 10%, 40%, and 0%, respectively. Susceptibilities of UU only to doxycycline, erythromycin, ciprofloxacin, and azithromycin were 94.8%, 87.9%, 5.2%, and 81%, respectively. Susceptibilities of both MH and UU to doxycycline, erythromycin, ciprofloxacin, and azithromycin were 97.2%, 5.6%, 11.1%, and 11.1%, respectively. CONCLUSION: UU only was the leading causative pathogen for genitourinary infection in our study. MH only accounted for about one sixth of UU only infections. Doxycycline was still the best antibiotics as most patients with MH only, UU only, or both MH and UU positive culture showed susceptibility. For ciprofloxacin, less than 12% of those with UU only and both MH and UU culture positive results showed susceptibility.
Anti-Bacterial Agents ; Azithromycin ; Ciprofloxacin ; Doxycycline ; Erythromycin ; Female ; Humans ; Medical Records ; Membranes ; Mycoplasma hominis ; Mycoplasma ; Obstetric Labor, Premature ; Pregnancy ; Pregnant Women ; Retrospective Studies ; Rupture ; Ureaplasma urealyticum ; Ureaplasma

Rapid diagnostic tests (RDTs) for malaria using antibodies against pan-Plasmodium antigen lactate dehydrogenase (pLDH) are commonly used for malaria diagnosis. The level of malaria parasitemia determined by peripheral blood smears (PBS) correlates with the pLDH concentration in most cases. We report a case of malaria recurrence associated with false-negative RDT results. A 22-year-old male patient was admitted to the Armed Forces Capital Hospital with fever and chills, and was diagnosed with malaria infection. Four days after antimalarial treatment, these symptoms recurred. After admitting to our hospital, doxycycline was administered for 4 days. Even after administration of doxycycline, the malaria parasites in blood smears remained positive, but RDT showed negative results. Therefore, for patients receiving doxycycline, serial blood smear testing should be performed to exclude false-negative malaria RDT results.
Antibodies ; Arm ; Chills ; Diagnosis ; Diagnostic Tests, Routine ; Doxycycline ; Fever ; Humans ; L-Lactate Dehydrogenase ; Malaria ; Male ; Parasitemia ; Parasites ; Recurrence ; Young Adult

Two manganese peroxidases (MnPs), MnP1 and MnP2, and a laccase, Lac1, were purified from Trametes polyzona KU-RNW027. Both MnPs showed high stability in organic solvents which triggered their activities. Metal ions activated both MnPs at certain concentrations. The two MnPs and Lac1, played important roles in dye degradation and pharmaceutical products deactivation in a redox mediator-free system. They completely degraded Remazol brilliant blue (25 mg/L) in 10–30 min and showed high degradation activities to Remazol navy blue and Remazol brilliant yellow, while Lac1 could remove 75% of Remazol red. These three purified enzymes effectively deactivated tetracycline, doxycycline, amoxicillin, and ciprofloxacin. Optimal reaction conditions were 50 °C and pH 4.5. The two MnPs were activated by organic solvents and metal ions, indicating the efficacy of using T. polyzona KU-RNW027 for bioremediation of aromatic compounds in environments polluted with organic solvents and metal ions with no need for redox mediator supplements.
Amoxicillin ; Biodegradation, Environmental ; Ciprofloxacin ; Doxycycline ; Hydrogen-Ion Concentration ; Ions ; Laccase ; Manganese ; Oxidation-Reduction ; Peroxidases ; Pharmaceutical Preparations ; Solvents ; Tetracycline ; Trametes

Anthrax, caused by Bacillus anthracis, is a non-contagious infectious disease that affects a wide range of animal species (primarily ruminants) including humans. Due to the often-fatal outcome in humans, quick administration of definitely effective antimicrobials is crucial either as prophylaxis or as a clinical case therapy. In this study, 110 B. anthracis strains, temporally, geographically, and genetically different, isolated during anthrax outbreaks in Italy from 1984 to 2017, were screened using a broth microdilution method to determine their susceptibility to 16 clinically relevant antimicrobial agents. The strains were isolated from various matrices (human, animal, and environmental samples) and were representative of thirty distinct genotypes previously identified by 15-loci multiple-locus variable-number of tandem repeats analysis. The antimicrobials tested were gentamicin, ceftriaxone, streptomycin, penicillin G, clindamycin, chloramphenicol, vancomycin, linezolid, cefotaxime, tetracycline, erythromycin, rifampin, amoxicillin, ciprofloxacin, doxycycline, and trimethoprim. All isolates were susceptible to most of the tested antimicrobials, with the exception of trimethoprim for which all of them showed high minimal inhibitory concentration values. An intermediate level of susceptibility was recorded for ceftriaxone and cefotaxime. Although the Centers for Disease Control and Prevention recommend the use of doxycycline, ciprofloxacin, penicillin G, and amoxicillin for treatment of human cases and for post-exposure prophylaxis to anthrax spores, this study shows a high degree of in vitro susceptibility of B. anthracis to many other antimicrobials, suggesting the possibility of an alternative choice for prophylaxis and therapy.
Amoxicillin ; Animals ; Anthrax ; Anti-Infective Agents ; Bacillus anthracis ; Bacillus ; Cefotaxime ; Ceftriaxone ; Centers for Disease Control and Prevention (U.S.) ; Chloramphenicol ; Ciprofloxacin ; Clindamycin ; Communicable Diseases ; Disease Outbreaks ; Doxycycline ; Erythromycin ; Genotype ; Gentamicins ; Humans ; In Vitro Techniques ; Italy ; Linezolid ; Methods ; Microbial Sensitivity Tests ; Penicillin G ; Post-Exposure Prophylaxis ; Rifampin ; Spores ; Streptomycin ; Tandem Repeat Sequences ; Tetracycline ; Trimethoprim ; Vancomycin

BACKGROUND AND OBJECTIVES: Recent studies have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF)-associated hospitalization and mortality in patients with diabetes. However, it is not clear whether SGLT2 inhibitors have a cardiovascular benefit in patients without diabetes. We aimed to determine whether empagliflozin (EMPA), an SGLT2 inhibitor, has a protective role in HF without diabetes. METHODS: Cardiomyopathy was induced in C57BL/6J mice using intraperitoneal injection of doxorubicin (Dox). Mice with HF were fed a normal chow diet (NCD) or an NCD containing 0.03% EMPA. Then we analyzed their phenotypes and performed in vitro experiments to reveal underlying mechanisms of the EMPA's effects. RESULTS: Mice fed NCD with EMPA showed improved heart function and reduced fibrosis. In vitro studies showed similar results. Phloridzin, a non-specific SGLT inhibitor, did not show any protective effect against Dox toxicity in H9C2 cells. SGLT2 inhibitor can cause increase in blood ketone levels. Beta hydroxybutyrate (βOHB), which is well known ketone body associated with SGLT2 inhibitor, showed a protective effect against Dox in H9C2 cells and in Dox-treated mice. These results suggest elevating βOHB might be a convincing mechanism for the protective effects of SGLT2 inhibitor. CONCLUSIONS: SGLT2 inhibitors have a protective effect in Dox-induced HF in mice. This implied that SGLT2 inhibitor therapy could be a good treatment strategy even in HF patients without diabetes.
3-Hydroxybutyric Acid ; Animals ; Cardiomyopathies ; Diet ; Doxorubicin ; Doxycycline ; Fibrosis ; Heart Failure ; Heart ; Hospitalization ; Humans ; In Vitro Techniques ; Injections, Intraperitoneal ; Mice ; Mortality ; Phenotype ; Phlorhizin