Combination Of Minocycline Research Articles

Clinical characteristics of pyoderma gangrenosum: Case series and literature review.

Pyoderma gangrenosum (PG) is a neutrophilic skin disease characterized by recurrent painful cutaneous ulcers, often accompanied by inflammatory bowel disease, joint pain, and other systemic damage. This disease is relatively rare in clinical practice and its diagnosis and treatment are often delayed, leading to secondary infections in the skin lesions, prolonged disease course, and increased disease burden on patients. This study retrospectively analyzed the clinical characteristics and treatment strategies of patients with PG admitted to our hospital and conducted a literature review, in order to improve the understanding of the disease among clinical doctors, enable patients to receive better diagnosis and treatment, and ultimately improve patient prognosis. Clinical data of patients diagnosed with PG and hospitalized in Beijing Chaoyang Hospital, Capital Medical University from January 2014 to December 2022 were retrospectively collected. The clinical manifestations, treatment strategies, efficacy, and disease outcomes were analyzed. A total of 14 patients, including 8 males and 6 females, aged 14 to 66 years, were included. Skin lesion types: 13 cases were ulcer-type, 1 case was pustule combined with ulcer-type, and the lower limbs were the most commonly affected areas. All the 14 patients presented with comorbidities. All patients were treated with glucocorticoids, with a daily dose equivalent to 20 to 100 mg prednisone and a median dose of 40 mg. Among them, 3 patients were treated with minocycline in combination, 1 patient was treated with mycophenolate mofetil 0.5 twice daily in combination, 1 patient was treated with cyclophosphamide 0.1 once daily in combination, and 1 patient was treated with thalidomide 0.1 every night in combination. PG is a relatively rare immune-related skin disease. Our small sample data analysis found that male PG is not uncommon in the Chinese population. Systemic glucocorticoids can quickly control the symptoms of PG in most patients with PG. In patients with poor efficacy or limited use of glucocorticoids, immunosuppressive drugs or novel targeted drugs such as biologics or small-molecule drugs should be used in combination as early as possible. Skin lesion care focuses on preventing infection, avoiding surgical debridement, and emphasizing pain management and the symptomatic treatment of comorbidities.

Efficacy and Safety of Antibiotics in the Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Infections: A Systematic Review and Network Meta-Analysis.

Vancomycin is a first-line drug for the treatment of MRSA infection. However, overuse of vancomycin can cause bacteria to become resistant, forming resistant strains and making infections more difficult to treat. This study aimed to evaluate the efficacy and safety of different antibiotics in the treatment of MRSA infections and to compare them, mainly with vancomycin, to find better vancomycin alternatives. All studies were obtained from the PubMed and Embase databases from inception to 13 April 2023. The three comprehensive indicators of clinical cure success rate, clinical microbiological success rate, and adverse reactions were evaluated, and the clinical cure success rates of three disease types, complex skin and skin structure infections (cSSSIs), complex skin and soft tissue infections (cSSTIs), and pneumonia, were analyzed in subgroups. All statistical analyses were performed using R and STATA 14.0 software for network meta-analysis. A total of 38 trials with 6281 patients were included, and 13 drug treatments were evaluated. For MRSA infections, the results of network meta-analysis showed that the clinical success rates of linezolid, the combination of vancomycin and rifampin, and the combination of minocycline and rifampin were better than that of vancomycin (RR 1.71; 95%-CI 1.45-2.02), (RR 2.46; 95%-CI 1.10-5.49) (RR, 2.77; 95%-CI 1.06-7.21). The success rate of clinical microbiological treatment with vancomycin was inferior to that with telavancin (RR 0.74; 95%-CI 0.55-0.99). Linezolid had a higher rate of adverse reactions than teicoplanin (RR 5.35; 95%-CI 1.10-25.98). Subgroup analysis showed that vancomycin had a lower clinical success rate than linezolid in the treatment of MRSA-induced cSSSIs, cSSTIs, and pneumonia (RR 0.59; 95%-CI 0.44-0.80) (RR 0.55; 95%-CI 0.35-0.89) (RR 0.55; 95%-CI 0.32-0.93). This systematic review and NMA provide a new comparison framework for the clinical treatment of MRSA infection. The NMA suggests that linezolid may be the antibiotic of choice for the treatment of MRSA infections, with the ability to improve clinical and microbiological success rates despite its disadvantage in terms of adverse effects. At the same time, the combination of minocycline and rifampicin may be the most effective drug to treat MRSA-induced cSSSIs, tedizolid may be the best drug to treat MRSA-induced cSSTIs, and the combination of vancomycin and rifampicin may be the most effective treatment for MRSA-induced pneumonia. More high-quality studies are still needed in the future to further identify alternatives to vancomycin. PROSPERO registration number CRD42023416788.

Synergy of polymyxin B and minocycline against KPC-3- and OXA-48-producing Klebsiella pneumoniae in dynamic time-kill experiments: agreement with in silico predictions.

Combination therapy is often used for carbapenem-resistant Gram-negative bacteria. We previously demonstrated synergy of polymyxin B and minocycline against carbapenem-resistant Klebsiella pneumoniae in static time-kill experiments and developed an in silico pharmacokinetic/pharmacodynamic (PK/PD) model. The present study assessed the synergistic potential of this antibiotic combination in dynamic experiments. Two clinical K. pneumoniae isolates producing KPC-3 and OXA-48 (polymyxin B MICs 0.5 and 8 mg/L, and minocycline MICs 1 and 8 mg/L, respectively) were included. Activities of the single drugs and the combination were assessed in 72 h dynamic time-kill experiments mimicking patient pharmacokinetics. Population analysis was performed every 12 h using plates containing antibiotics at 4× and 8× MIC. WGS was applied to reveal resistance genes and mutations. The combination showed synergistic and bactericidal effects against the KPC-3-producing strain from 12 h onwards. Subpopulations with decreased susceptibility to polymyxin B were frequently detected after single-drug exposures but not with the combination. Against the OXA-48-producing strain, synergy was observed between 4 and 8 h and was followed by regrowth. Subpopulations with decreased susceptibility to polymyxin B and minocycline were detected throughout experiments. For both strains, the observed antibacterial activities showed overall agreement with the in silico predictions. Polymyxin B and minocycline in combination showed synergistic effects, mainly against the KPC-3-producing K. pneumoniae. The agreement between the experimental results and in silico predictions supports the use of PK/PD models based on static time-kill data to predict the activity of antibiotic combinations at dynamic drug concentrations.

Efficacy of the combination of minocycline and periodontal basic therapy in type 2 diabetes mellitus patients with chronic periodontitis

Purpose: To investigate the clinical efficacy of the combination of minocycline and periodontal basic treatment on type 2 diabetes mellitus (T2DM) patients with chronic periodontitis (CP) and its impact on inflammatory factors.
 Methods: A total of 90 T2DM patients with CP admitted to the Department of Stomatology in Hainan Medical College Second Affiliated Hospital, China from January 2020 to October 2022, were enrolled in this study and randomly assigned to two equal groups, viz, study and control group. Study group received minocycline in addition to routine hypoglycemic control and basic periodontal treatment, while control group received only routine hypoglycemic control and basic periodontal treatment. Treatment lasted for 8 weeks. Efficacy of the combination of minocycline and periodontal basic treatment of T2DM patients with CP in the two groups, as well as the periodontal probing depth (PD), clinical attachment loss (CAL), bleeding on probing (sulcus bleeding index, SBI), interleukin-36 (IL-36), interleukin-1β (IL1β), tumor necrosis factor-α (TNF-α), glycated hemoglobin (HbA1c) level, chewing function score, Oral Health Impact Profile-14 (OHIP-14) score, and incidence of adverse reactions before and after treatment were determined.
 Results: The effectiveness/efficacy of treatment in study group (91.11 %) was significantly higher than in control group (75.56 %, p < 0.05). After treatment, study group had reduced PD, PLI, and SBI scores than control group (p < 0.05). Study group also showed lower levels of IL-1β, IL-36, and TNF-α as well as reduced OHIP-14 score and a higher chewing function score than control group (p < 0.05).
 Conclusion: The combination of minocycline with periodontal basic treatment improves the efficacy in T2DM patients with CP, and reduces the level of inflammatory factors with a good margin of safety.

A randomised double-blind placebo-controlled trial of minocycline and/or omega-3 fatty acids added to treatment as usual for at risk Mental States: The NAYAB study

BackgroundInflammatory mechanisms are thought to contribute to the onset of psychosis in persons with an at-risk mental state (ARMS). We investigated whether the anti-inflammatory properties of minocycline and omega-3 polyunsaturated fatty acids (omega-3), alone or synergistically, would prevent transition to psychosis in ARMS in a randomised, double-blind, placebo-controlled trial in Pakistan. Methods10,173 help-seeking individuals aged 16–35 years were screened using the Prodromal Questionaire-16. Individuals scoring 6 and over were interviewed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to confirm ARMS. Participants (n = 326) were randomised to minocycline, omega-3, combined minocycline and omega-3 or to double placebo for 6 months. The primary outcome was transition to psychosis at 12 months. FindingsForty-five (13.8 %) participants transitioned to psychosis. The risk of transition was greater in those randomised to omega-3 alone or in combination with minocycline (17.3.%), compared to 10.4 % in those not exposed to omega-3; a risk-ratio (RR) of 1.67, 95 % CI [0.95, 2.92] p = 0.07. The RR for transitions on minocycline vs. no minocycline was 0.86, 95 % CI [0.50, 1.49] p > 0.10. In participants who did not become psychotic, CAARMS and depression symptom scores were reduced at six and twelve months (mean CAARMS difference = 1.43; 95 % CI [0.33, 1.76] p < 0.01 in those exposed to omega-3. Minocycline did not affect CAARMS or depression scores. InterpretationIn keeping with other studies, omega-3 appears to have beneficial effects on ARMS and mood symptom severity but it increased transition to psychosis, which may reflect metabolic or developmental consequences of chronic poor nutrition in the population. Transition to psychosis was too rare to reveal a preventative effect of minocycline but minocycline did not improve symptom severity. ARMS symptom severity and transition to psychosis appear to have distinct pathogeneses which are differentially modulated by omega-3 supplementation. FundingThe study was funded by the Stanley Research Medical Institute.

Abstract 2687: The combination of temozolomide and minocycline for the treatment of glioblastoma

Abstract Glioblastoma multiforme (GBM) is the most prevalent and aggressive form of malignant brain tumor and accounts for 49.1% of all central nervous system tumors. Current methods of therapy remain minimally successful as survival rate remains low (only 6.8% of patients surviving 5 years post-diagnosis). Thus, there is a great need to design alternative treatment methods for patients with GBM. Temozolomide (TMZ) is a chemotherapeutic treatment and a first line treatment option for GBM as it has been shown to increase survival time. Minocycline (MINO) is commonly used for its antibiotic properties but has also been proven to have antiangiogenic effects for GBM treatment. The objective of this study was to investigate the additive effects of MINO and TMZ in both GBM (U87) and human umbilical vein endothelial cells (HUVEC) for the treatment of GBM. We hypothesized that the combination of MINO and TMZ will result in lower cell viability and higher protein levels of apoptosis and autophagy markers) compared to the drugs alone and therefore, will be more effective at treating GBM. In this study, U87 and HUVEC cells were treated with MINO and TMZ alone or in combination and a MTT assay was used to determine cell viability by measuring absorbance (570 nm) with a microplate reader. The IC50 values of the drugs were determined from the dose-response curves using GraphPad to compare the sensitivity of each cell line to the drugs. Protein levels of apoptosis (Cas3, PARP) and autophagy (LC3B) markers were determined after treatment of U87 cells with MINO and TMZ alone or in combination using immunoblotting. β-actin was used as a loading control and 0.5% dimethyl sulfoxide was used as a positive autophagy control. Protein bands were detected and visualized with enhanced chemiluminescence reagents. The IC50 of MINO and TMZ were found to be 1688 µM and 1913 µM in U87 cells, and 247 µM and 1162 µM in HUVEC cells, respectively. Although glioma cells result in autophagy and apoptosis when exposed to MINO, MINO’s anti-angiogenic effect may have resulted in heightened sensitivity in HUVEC cells. U87 cells exposed to MINO (1000 µM) resulted in a cell viability of 61% and TMZ (1200 µM) resulted in 60%, while the combination of both drugs resulted in 43% cell viability. HUVEC cells exposed to MINO (200 µM) resulted in a cell viability of 64% and TMZ (30 µM) resulted in 84%, while the combination of both drugs resulted in 44% cell viability, resulting in additive effects for both cell lines. Preliminary results for protein expression analysis show similar expression of apoptotic and autophagy markers in samples with individual and combined drug treatments. In conclusion, this study demonstrated that the combination of MINO and TMZ resulted in additive effects compared to each drug alone and thus, the dual delivery of both drugs from a local delivery system may be a promising therapy for GBM. Citation Format: Marco A. Arriaga, Natasha Garcia-Rodriguez, Andrea Ramirez, Sue Anne Chew. The combination of temozolomide and minocycline for the treatment of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2687.

Comparing the clinical effects of local administration of minocycline ointment and doxycycline solution in the treatment of acute periodontal abscesses: a retrospective clinical study.

The objective of this retrospective clinical study was to provide evidence supporting the adjunctive local application of doxycycline solution or minocycline ointment, in conjunction with drainage, for the treatment of acute periodontal abscesses. The study included 63 patients who had received treatment for acute periodontal abscesses through drainage supplemented with 1 of 3 types of adjunctive medications during their initial visit (visit 1; baseline): 1) saline irrigation (the control group), 2) 2% minocycline ointment (the TM group), or 3) 300 mg/mL doxycycline irrigation (the TD group). The same adjunctive medication was administered at visit 2, which took place 1 week after visit 1. Probing depth (PD), bleeding on probing (BOP), plaque index, gingival recession, clinical attachment level, and tooth mobility were clinically evaluated at visits 1, 2, and a third visit (visit 3; 4 weeks after visit 1). Statistical significance was considered to be indicated by P values <0.05. By visit 3, all clinical indices and tooth mobility had significantly decreased in each group. At this visit, PD and BOP on the abscess side were significantly lower in the TM and TD groups compared to the control group. The TD group showed a significantly greater improvement than the TM group, with mean PD reductions of 1.09 mm in the control group, 1.88 mm in the TM group, and 2.88 mm in the TD group. Similarly, mean BOP reductions were 45% in the control group, 73.02% in the TM group, and 95.45% in the TD group. Local and adjunctive administration of doxycycline and minocycline in combination with drainage exhibited clinical advantages over drainage alone in improving PD and BOP. Notably, a doxycycline solution of 300 mg/mL was more effective than a 2% minocycline ointment.

The use of antimicrobial biomaterials as a savior from post-operative vascular graft-related infections: A review

Cardiovascular diseases rank first in mortality and morbidity. There are various treatments for replacing a blood vessel artificially, such as autologous graft implantation, bio-engineered vascular graft implantation, etc. Due to the external medical intervention or immunocompromised state in the patients, there are high chances of septic infection at the site of implantation. This increases the risk of blood-related infections in these patients. Thus, it is imperative to avoid the spread of infection and to destroy the infection-causing microorganisms by incorporating an antimicrobial agent in the implantable biomaterial. For instance, use combination of minocycline, chlorhexidine, and rifampin was impregnated on Dacron, and PTFE (polytetrafluoroethylene) vascular grafts showed a 100% patency rate and increased antibiotic activity than the counterparts. This review summarises various methods of incorporating antimicrobial agents in the biomaterial for developing an antimicrobial vascular graft.

Approach of Persisters Relapse in a Smear-negative Leprosy after Second MB-MDT Completion: An Arduous Case Report

Introduction: Many infectious disease intervention programs, including leprosy, are cautious about the establishment of relapse and drug resistance. This case report reports on a male patient who has had two relapses and had undergone twice MB-MDT treatment as well.&#x0D; Case Report: A 31 year-old male, came with the main complaint of new hypopigmented patches appeared on the body since 4 months ago, which arose from his second MB-MDT treatment. He started his first MB-MDT treatment in 2019 and second MD-MDT in 2020. Slit skin smear yielded negative results and histopathological examination showed no signs of leprosy. Serological anti-PGL-1 antibody tests yielded very high IgM (3.163) and normal IgG (2) levels. PCR amplification examination showed positive, but DNA sequencing targeting rpoB, folP, and gyrA genes showed no mutations. He was diagnosed with persisters relapse in a borderline-lepromatous leprosy and was treated with rifampicin 600 mg/day for 2 weeks; combination of minocycline 100 mg/ day, clarithromycin 500 mg/ day, and clofazimine 50 mg/ day for 6 months; and methylprednisolone 32 mg/ day for the neuritis. No new lesions appeared during current treatment and he is also showing gradual improvement of foot drop in his left leg.&#x0D; Discussion: The fact of a very high IgM levels after 2 courses of MB-MDT indicated that there is still bacteria that continued to induce antibody formation, thus supporting the persisters bacilli hypothesis in this case. Positive results of PCR amplification conclude that there is still M. leprae bacilli in skin tissues, which may be hidden in deeper tissues. We have to make a more proactive approach considering this was his second times of relapse, and knowing the fact that MB-MDT was consumed religiously in the two previous treatment.&#x0D; Conclusion: In an arduous case like this, proactive step must be taken. Whenever possible, the use of whole genome sequencing is strongly advised.&#x0D; Keywords: leprosy, persisters bacilli, relapse, drug resistance

Abstract 1744: Injectable alginate scaffolds for the dual delivery of Minocycline and Temozolomide for the treatment of glioblastoma

Abstract Glioblastoma Multiforme (GBM) is the most frequent and aggressive malignant primary brain tumor in adults with a life expectancy of less than fifteen months after diagnosis. The standard care for GBM includes surgical resection followed by radiotherapy and chemotherapy. Despite advances in the different methods of therapy, the prognosis for gliomas has not been dramatically improved through the years due to high levels of reoccurrence therefore, alternative treatment methods are needed for GBM. Minocycline (MINO) is a common antibiotic with potential anticancer effects by acting as an anti-angiogenic agent which can help in the treatment and reduction of gliomas by reducing blood vessel formation. Temozolomide (TMZ) is a chemotherapy alkylating agent that has demonstrated antitumor activity against highly resistant malignancies as high-grade gliomas. Injectable alginate scaffolds can serve as a local delivery system for controlled drug release and can be an important component for the development of a treatment method against GBM. The objective of this study was to investigate the optimal concentration of TMZ and MINO alone or in combination against glioblastoma cells (U87-MG) and human umbilical vein endothelial cells (HUVEC) and to evaluate the ability of an injectable alginate scaffold to control the rate of drug release for the treatment of GBM. In this study, U87-MG were treated with MINO (0-4000 µM) and TMZ (0-6000 µM), while HUVEC were treated with MINO (0-1000 µM) and TMZ (0-2000 µM) alone or in combination and a MTT assay was used to determine cell viability. Injectable alginate scaffolds were fabricated by dissolving sodium alginate and calcium carbonate in water and then homogenized with glucanolactone and drugs for 20 seconds. The mixture was then injected into a 24-well plate. After fabrication, scaffolds with MINO, TMZ and MINO/TMZ were incubated in PBS at 37 °C. At each timepoint (1, 4, 7, 10 and 14 days), the amount of drug released was measured by reading the absorbance of MINO and TMZ at 350 and 327 nm, respectively using a microplate reader. The 50% inhibitory concentration (IC50) of MINO and TMZ were found to be 950 µM and 900 µM, respectively in U87-MG. In HUVEC, the IC50 of MINO and TMZ were found to be 150 µM and 400 µM, respectively. MINO and TMZ alone reduced cell viability by 39% and 41%, respectively, in U87-MG and in HUVEC by 36% and 34%, respectively. In combination, both drugs reduced cell viability in U87-MG by 58% and in HUVEC by 56%, resulting in synergistic effects for both cell lines. In addition, the application of the injectable alginate scaffold resulted in a controlled release of the drugs alone or in combination. In conclusion, the combination of MINO and TMZ resulted in synergistic effects on cell viability in both cell lines and the controlled delivery of both drugs with an injectable scaffold can be a promising method for the treatment of GBM. Citation Format: Marco A. Arriaga, Rene N. Rico, Kaitlyn D. Ybanez, Daniela Lopez-Lorenzo, Sue Anne Chew. Injectable alginate scaffolds for the dual delivery of Minocycline and Temozolomide for the treatment of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1744.

In vitro Antibacterial Activity and Resistance Prevention of Antimicrobial Combinations for Dihydropteroate Synthase-Carrying Stenotrophomonas maltophilia.

BackgroundStenotrophomonas maltophilia (S. maltophilia) is a multidrug-resistant gram-negative bacillus that is known to be an opportunistic pathogen, particularly in a hospital environment. The infection has a high morbidity and mortality. Sulfamethoxazole-trimethoprim (SXT) is the first-line agent recommended for its treatment. The global spread of dihydropteroate synthase (sul) genes has resulted in an increased resistance rate. However, the appropriate therapy for infections caused by sul-carrying S. maltophilia has not yet been established.ObjectiveOur study aimed to identify the optimal antibiotic combinations that could both show high antibacterial activity against sul-carrying S. maltophilia and the ability to prevent the emergence of resistance at clinical dosage regimens.MethodsTime-killing experiments and mutant prevention concentration (MPC) experiments were conducted to evaluate the antibacterial effect and ability to prevent resistance to minocycline, tigecycline, moxifloxacin, and ticarcillin/clavulanic acid (T/K), both alone and in combination, at clinically relevant antimicrobial concentrations.ResultsMinocycline, tigecycline, and T/K all exhibited bacteriostatic activity to sul-carrying S. maltophilia. The combination of minocycline plus T/K and tigecycline plus T/K neither enhanced the bactericidal ability nor prevented drug-resistant mutations. Moxifloxacin, at 2 mg/L, showed good bactericidal activity to most S. maltophilia, but bacterial regrowth at 24 h was observed in two strains. When combined with T/K, moxifloxacin showed good bactericidal activity in all moxifloxacin-sensitive strains. The concentrations of moxifloxacin alone were lower than most MPCs of the tested sul-carrying strains. When combined with T/K, the mean steady-state concentrations (MSC) of moxifloxacin could prevent 70% of resistance, and the peak concentration (Cmax) prevented 95% of resistance.ConclusionThe combination of moxifloxacin and T/K can achieve a good in vitro bactericidal effect and prevent the emergence of resistance at clinical dosage regimens, and may be an optimal therapeutic strategy for S. maltophilia infections, especially for vulnerable immunocompromised and critically ill patients.

Polymyxin B Combined with Minocycline: A Potentially Effective Combination against blaOXA-23-harboring CRAB in In Vitro PK/PD Model.

Polymyxin-based combination therapy is commonly used to treat carbapenem-resistant Acinetobacter baumannii (CRAB) infections. In the present study, the bactericidal effect of polymyxin B and minocycline combination was tested in three CRAB strains containing blaOXA-23 by the checkerboard assay and in vitro dynamic pharmacokinetics/pharmacodynamics (PK/PD) model. The combination showed synergistic or partial synergistic effect (fractional inhibitory concentration index ≤0.56) on the tested strains in checkboard assays. The antibacterial activity was enhanced in the combination group compared with either monotherapy in in vitro PK/PD model. The combination regimen (simultaneous infusion of 0.75 mg/kg polymyxin B and 100 mg minocycline via 2 h infusion) reduced bacterial colony counts by 0.9–3.5 log10 colony forming units per milliliter (CFU/mL) compared with either drug alone at 24 h. In conclusion, 0.75 mg/kg polymyxin B combined with 100 mg minocycline via 2 h infusion could be a promising treatment option for CRAB bloodstream infections.

Treatment of resistant granuloma annulare with rifampin, norfloxacin, and minocycline combination therapy.

article: Treatment of resistant granuloma annulare with rifampin, norfloxacin, and minocycline combination therapy - Italian Journal of Dermatology and Venereology 2021 December;156(Suppl. 1 to No. 6):28-9 - Minerva Medica - Journals

Potential of Favipiravir and Minocycline Combination Therapy for COVID-19

Potential of Favipiravir and Minocycline Combination Therapy for COVID-19

In vitro synergistic effect of minocycline combined with antifungals against Cryptococcus neoformans

BackgroundCryptococcus neoformans infections occur in immunocompromised patients, especially those with HIV infection, chemoradiotherapy after cancer, and organ transplantation. Infection can cause pneumonia and meningoencephalitis in severe cases with a high mortality rate if not treated. Although fluconazole and amphotericin B are the first-line treatments for cryptococcosis, the rate of fluconazole resistance has increased significantly due to long-term use. Minocycline is a derivative of tetracycline that exerts its antibacterial effect through inhibition of bacterial protein synthesis. It is also able to pass the blood-brain barrier to act on the central nervous system. The present study investigates the effects of minocycline in combination with antifungals in treating C. neoformans. ObjectiveTo determine in vitro interactions of minocycline combined with itraconazole, voriconazole, posaconazole, fluconazole and amphotericin B against C. neoformans. MethodsThe minimum inhibitory concentrations (MIC) of the antifungals were determined by the CLSI Clinical and Laboratory Standards Institute M27-A3 microdilution method. The in vitro synergistic effects of minocycline combined with itraconazole, voriconazole, posaconazole, fluconazole, and amphotericin B on C. neoformans were detected by the broth microdilution checkerboard technique and disk diffusion testing. Results and ConclusionThe working concentration ranges were 0.125–4 µg/mL for itraconazole, 0.03–0.125 µg/ml for voriconazole, 0.03–1 µg/ml for posaconazole, 0.25–16 µg/ml for fluconazole, and 0.125–2 µg/ml for amphotericin B. The synergistic rates of minocycline combinations against C. neoformans were 55% with itraconazole, 10% with voriconazole, 85% with posaconazole, 20% with fluconazole, and 70% with amphotericin B. The effective MIC value of minocycline in the synergistic combination decreased to 2–32 µg/ml, while the MIC of itraconazole decreased to 0.03–0.125 µg/ml, voriconazole 0.03–0.125 µg/ml, posaconazole 0.03–0.125 µg/ml, 0.125–4 µg/ml fluconazole, and 0.06–0.50 µg/ml amphotericin B. The disk diffusion assay showed that the plates containing minocycline and antifungal drugs produced inhibition zones with diameters larger than the single drug plates. Minocycline showed no antagonistic effect in the combinations. In conclusion, the combination of minocycline and azoles or amphotericin B has synergistic effects against C. neoformans in vitro.

Novel design and combination strategy of minocycline and OECs-loaded CeO2 nanoparticles with SF for the treatment of spinal cord injury: In vitro and in vivo evaluations

Abstract Generally, several mechanisms influenced the secondary injury chutes following acute spinal cord injury (SCI). Though current SCI therapeutic approaches mostly target single elements in the injury chutes, they have been mostly ineffective in clinical trials. The aim of this study was to design and develop a novel cerium oxide/silk fibroin (CeO2/SF) hydrogel material loaded with minocycline (MCN) and transplantation of olfactory ensheathing cells (OEC) for SCI treatment. The prepared CeO2/SF hydrogel has an advantageous porous morphological structure and CeO2 NPs were greatly encapsulated on the surface, which was confirmed by microscopic observations. The results of in vitro analyses established favourable biocompatibility of 94.65% and 89.45%, sustained drug release rate of 89% and 58%, and significant reduction in pro-inflammatory factors for the treatments using cerium oxide loaded silk fibroin (CSF) and CeO2 NPs, respectively. Meanwhile, the administration of MCN@OEC greatly provides an efficient improvement in BBB score, decreased bladder weight, and histological improvement after SCI when compared to the control. Therefore, the combined MCN and OEC-loaded CSF hydrogel sample could be proved as a low cost, safe, and potential material for the treatment of SCI.

Effects Of Minocycline Combined With Tinidazole For Treatment Of Chronic Periodontitis.

Purpose: To investigate the therapeutic effects of minocycline combined with tinidazole in the treatment of chronic periodontitis (CP). Methods: Seventy-three CP patients treated May 2018–December 2019 at Yuyao People’s Hospital (Yuyao, China) were enrolled in this study: 34 were treated with minocycline alone (control group; CG) and 39 were treated with a combination of minocycline and tinidazole (observation group; OG). Both groups were treated continuously for four weeks and plaque index (PLI), bleeding index (BI), periodontal pocket depth (PD), periodontal attachment level (PAL) and alveolar bone height were compared before and after treatment. Pain was evaluated using the visual analogue scale (VAS). Levels of TNF-α and IL-6 before and after treatment were determined using an enzyme-linked immunosorbent assay. Adverse reactions were compared. Results: In each group, PLI, BI, PD, PAL and alveolar bone height were lower after treatment (P<0.05), and those in OG were lower than those in CG (P<0.05). TNF-α and IL-6 levels in both groups were lower after treatment (P<0.05), and the levels in serum of the OG were lower than those of the CG (P<0.05). After treatment, the VAS in OG was lower than that of CG (P<0.05). There was no significant difference in adverse reactions between groups (P>0.05). Conclusion: Minocycline combined with tinidazole was more effective in treating CP than minocycline alone. This drug combination improved the periodontal indexes and inflammatory reaction of CP and relieved their pain. No significant difference in adverse reactions was seen.

Delayed dosing of minocycline plus N-acetylcysteine reduces neurodegeneration in distal brain regions and restores spatial memory after experimental traumatic brain injury

Multiple drugs to treat traumatic brain injury (TBI) have failed clinical trials. Most drugs lose efficacy as the time interval increases between injury and treatment onset. Insufficient therapeutic time window is a major reason underlying failure in clinical trials. Few drugs have been developed with therapeutic time windows sufficiently long enough to treat TBI because little is known about which brain functions can be targeted if therapy is delayed hours to days after injury. We identified multiple injury parameters that are improved by first initiating treatment with the drug combination minocycline (MINO) plus N-acetylcysteine (NAC) at 72 h after injury (MN72) in a mouse closed head injury (CHI) experimental TBI model. CHI produces spatial memory deficits resulting in impaired performance on Barnes maze, hippocampal neuronal loss, and bilateral damage to hippocampal neurons, dendrites, spines and synapses. MN72 treatment restores Barnes maze acquisition and retention, protects against hippocampal neuronal loss, limits damage to dendrites, spines and synapses, and accelerates recovery of microtubule associated protein 2 (MAP2) expression, a key protein in maintaining proper dendritic architecture and synapse density. These data show that in addition to the structural integrity of the dendritic arbor, spine and synapse density can be successfully targeted with drugs first dosed days after injury. Retention of substantial drug efficacy even when first dosed 72 h after injury makes MINO plus NAC a promising candidate to treat clinical TBI.

The Microglial Activation Inhibitor Minocycline, Used Alone and in Combination with Duloxetine, Attenuates Pain Caused by Oxaliplatin in Mice.

The antitumor drug, oxaliplatin, induces neuropathic pain, which is resistant to available analgesics, and novel mechanism-based therapies are being evaluated for this debilitating condition. Since activated microglia, impaired serotonergic and noradrenergic neurotransmission and overexpressed sodium channels are implicated in oxaliplatin-induced pain, this in vivo study assessed the effect of minocycline, a microglial activation inhibitor used alone or in combination with ambroxol, a sodium channel blocker, or duloxetine, a serotonin and noradrenaline reuptake inhibitor, on oxaliplatin-induced tactile allodynia and cold hyperalgesia. To induce neuropathic pain, a single dose (10 mg/kg) of intraperitoneal oxaliplatin was used. The mechanical and cold pain thresholds were assessed using mouse von Frey and cold plate tests, respectively. On the day of oxaliplatin administration, only duloxetine (30 mg/kg) and minocycline (100 mg/kg) used alone attenuated both tactile allodynia and cold hyperalgesia 1 h and 6 h after administration. Minocycline (50 mg/kg), duloxetine (10 mg/kg) and combined minocycline + duloxetine influenced only tactile allodynia. Seven days after oxaliplatin, tactile allodynia (but not cold hyperalgesia) was attenuated by minocycline (100 mg/kg), duloxetine (30 mg/kg) and combined minocycline and duloxetine. These results indicate a potential usefulness of minocycline used alone or combination with duloxetine in the treatment of oxaliplatin-induced pain.

Antimicrobial Effects of Minocycline, Tigecycline, Ciprofloxacin, and Levofloxacin against Elizabethkingia anophelis Using In Vitro Time-Kill Assays and In Vivo Zebrafish Animal Models

Elizabethkingia anophelis is a multidrug-resistant pathogen. This study evaluated the antimicrobial activity of minocycline, tigecycline, ciprofloxacin, and levofloxacin using in vitro time-kill assays and in vivo zebrafish animal models. The E. anophelis strain ED853-49 was arbitrarily selected from a bacterial collection which was concomitantly susceptible to minocycline, tigecycline, ciprofloxacin, and levofloxacin. The antibacterial activities of single agents at 0.5–4 × minimum inhibitory concentration (MIC) and dual-agent combinations at 2 × MIC using time-kill assays were investigated. The therapeutic effects of antibiotics in E. anophelis-infected zebrafish were examined. Both minocycline and tigecycline demonstrated bacteriostatic effects but no bactericidal effect. Minocycline at concentrations ≥2 × MIC and tigecycline at concentrations ≥3 × MIC exhibited a long-standing inhibitory effect for 48 h. Bactericidal effects were observed at ciprofloxacin and levofloxacin concentrations of ≥3 × MIC within 24 h of initial inoculation. Rapid regrowth of E. anophelis occurred after the initial killing phase when ciprofloxacin was used, regardless of the concentration. Levofloxacin treatment at the concentration of ≥2 × MIC consistently resulted in the long-lasting and sustainable inhibition of bacterial growth for 48 h. The addition of minocycline or tigecycline weakened the killing effect of fluoroquinolones during the first 10 h. The minocycline-ciprofloxacin or minocycline–levofloxacin combinations achieved the lowest colony-forming unit counts at 48 h. Zebrafish treated with minocycline or a combination of minocycline and levofloxacin had the highest survival rate (70%). The results of these in vitro and in vivo studies suggest that the combination of minocycline and levofloxacin is the most effective therapy approach for E. anophelis infection.