Combination Antiviral Therapy for Cytomegalovirus Disease in Patients with AIDS

1997 ◽  
Vol 31 (9) ◽  
pp. 1080-1082 ◽  
Author(s):  
Julie J Cline ◽  
Anna D Garrett
Keyword(s):  
Combination Therapy ◽  
Combined Therapy ◽  
In Vivo Studies ◽  
Combination Regimen ◽  
Synergistic Activity ◽  
Therapy Regimen ◽  
Superior Efficacy ◽  
Multiple Drugs

Currently, combination therapy with ganciclovir and foscarnet should be reserved for patients with disease progression while receiving monotherapy or for those who are unresponsive to either agent alone. Although cidofovir and ganciclovir were shown to have synergistic activity against human CMV in vitro, there have been no in vivo studies to confirm this activity. Therefore, if a combination regimen is necessary to control CMV in a patient, foscarnet and ganciclovir should be used first. There are several advantages of the combination therapy regimen. For instance, lower doses of the individual agents can be used with superior efficacy to monotherapy and similar toxicities.5,10 Also, for neurologic CMV involvement, the combination therapy may be superior to monotherapy because of the variable CSF penetration of either drug alone. In addition, combined therapy may be beneficial in treating and/or preventing drug-resistant strains of CMV.13 Even though combination therapy has evidence of superior efficacy compared with monotherapy in the treatment of CMV, several issues must be considered. First, combination therapy has longer administration times because of the infusion of multiple drugs, which may be an inconvenience. Also, even though the toxic effects are similar with both combined therapy and monotherapy, the adverse effects associated with combination therapy may be less well tolerated and may negatively affect the patient's quality of life. Finally, combination therapy is more expensive than monotherapy with ganciclovir or foscarnet alone.10 Patients should be evaluated with these issues in mind before combination therapy is initiated.

scholarly journals The Antitumor Activity of Sodium Selenite Alone and in Combination with Gemcitabine in Pancreatic Cancer: An In Vitro and In Vivo Study

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3169
Author(s):  
Kevin Doello ◽  
Cristina Mesas ◽  
Francisco Quiñonero ◽  
Gloria Perazzoli ◽  
Laura Cabeza ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Sodium Selenite ◽  
Molecular Mechanisms ◽  
Combined Therapy ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
C57bl Mice ◽  
Migration Capacity

Sodium selenite acts by depleting enzymes that protect against cellular oxidative stress. To determine its effect alone or in combination with gemcitabine (GMZ) in pancreatic cancer, we used PANC-1 and Pan02 cell lines and C57BL mice bearing a Pan02-generated tumor. Our results demonstrated a significant inhibition of pancreatic cancer cell viability with the use of sodium selenite alone and a synergistic effect when associated with GMZ. The molecular mechanisms of the antitumor effect of sodium selenite alone involved apoptosis-inducing factor (AIF) and the expression of phospho-p38 in the combined therapy. In addition, sodium selenite alone and in association with GMZ significantly decreased the migration capacity and colony-forming ability, reduced tumor activity in multicellular tumor spheroids (MTS) and decreased sphere formation of cancer stem cells. In vivo studies demonstrated that combined therapy not only inhibited tumor growth (65%) compared to the untreated group but also relative to sodium selenite or GMZ used as monotherapy (up to 40%), increasing mice survival. These results were supported by the analysis of C57BL/6 albino mice bearing a Pan02-generated tumor, using the IVIS system. In conclusion, our results showed that sodium selenite is a potential agent for the improvement in the treatment of pancreatic cancer and should be considered for future human clinical trials.

scholarly journals Novel T7-modified pH-responsive targeted nanosystem for co-delivery of docetaxel and curcumin in the treatment of esophageal cancer

2020 ◽  
Author(s):  
Lian Deng ◽  
Xiongjie Zhu ◽  
Zhongjian Yu ◽  
Ying Li ◽  
Lingyu Qin ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Side Effects ◽  
High Efficiency ◽  
In Vivo Studies ◽  
Ph Responsive ◽  
Therapeutic Platform ◽  
Multiple Drugs ◽  
Esophageal Cancer Cells

Abstract Although single-drug chemotherapy is still an effective treatment for esophageal cancer, its long-term application is limited by severe side effects. Nanomedicines have increasingly attracted attention because of their good biological safety, targeting and high-efficiency loading of multiple drugs. Herein, we have developed a pH-responsive nanocarrier that has high affinity for the transferrin receptor, which is overexpressed by tumor cells. The system is capable of simultaneous delivery of the chemotherapy drug, docetaxel, and the Chinese Medicine, curcumin, for treatment of esophageal cancer. This novel T7-modified targeting nanosystem releases loaded drugs when exposed to the acidic microenvironment of the tumor, and exerts a synergistic anti-tumor effect, and T7-NP-DC with docetaxel and curcumin loading of 10% and 6.1%, respectively. In vitro and in vivo studies showed that improved anti-tumor efficacy could be obtained by loading docetaxel and curcumin into the T7-modified nanocarrierwithout obvious toxicity or side effects, compared to drug without nanocarrier. Furthermore, the nanocarriers conjugated with T7 short peptides were more readily taken up by esophageal cancer cells compared with normal cells.Together, our findings indicate that the materials can safely exert synergistic anti-tumor effects and provide an excellent therapeutic platform for combination therapy of esophageal cancer.

Arsenic Trioxide Shows Synergistic Anti-Myeloma Effects When Combined with Bortezomib and Melphalan In Vitro and Helps Overcome Resistance of Multiple Myeloma Cells to These Treatments in Vivo.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2467-2467
Author(s):  
Richard A. Campbell ◽  
Haiming Chen ◽  
Daocheng Zhu ◽  
Janice C. Santos ◽  
Benjamin Bonavida ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Cell Lines ◽  
Combined Therapy ◽  
In Vivo Studies ◽  
Low Doses ◽  
Drug Resistant ◽  
Early Results ◽  
Post Implantation

Abstract Arsenic trioxide (ATO) induces apoptosis of plasma cells through a number of mechanisms including inhibiting DNA binding by NF-κB. These results suggest that this agent may be synergistic when combined with other active anti-myeloma drugs. To evaluate this we examined the effect of ATO alone and in combination with anti-myeloma treatments evaluated in vitro with MTT assays and using our severe combined immunodeficient (SCID)-hu murine myeloma models. First, we determined the effects of combining ATO with bortezomib or melphalan on the myeloma cell lines RPMI8226 and U266. Cell proliferation assays demonstrated marked synergistic anti-proliferative effects of ATO at concentrations ranging from 5x10−5M – 5x10−9M and melphalan concentrations ranging from 3x10−5M – 3x10−9M. Similar effects were observed when these cell lines were treated with bortezomib and varying concentrations of ATO (5x10−5 M – 5x10−10 M). We also investigated the potential of ATO to increase the efficacy of anti-myeloma therapies in our SCID-hu murine model LAGλ–1 (Yang H et al. Blood 2002). Each SCID mouse was implanted with a 0.5 cm3 LAGλ–1 tumor fragment into the left hind limb muscle. Mice were treated with ATO alone at 6.0 mg/kg, 1.25 mg/kg, 0.25 mg/kg, and 0.05 mg/kg intraperitoneally (IP) daily x5/week starting 19 days post-implantation. Mice receiving the highest dose of ATO (6.0 mg/kg) showed marked inhibition of tumor growth and reduction of paraprotein levels while there was no effect observed in all other treatment groups. Next, 27 days following implantation of our LAGλ–1 intramuscular (IM) tumor, LAGλ–1 mice were treated with ATO (1.25 mg/kg) IP, bortezomib (0.25 mg/kg), or the combination of both drugs at these doses in the schedules outlined above. ATO or bortezomib treatment alone had no anti-myeloma effects at these low doses consistent with our previous results whereas there was a marked decrease in both tumor volume (57%) and paraprotein levels (53%) in mice receiving the combined therapy. The combination of melphalan and ATO was also evaluated in this model. LAGλ–1 bearing mice received therapy with melphalan IP x1/weekly at 12.0 mg/kg, 6.0 mg/kg, 0.6 mg/kg, and 0.06 mg/kg starting 22 days post-implantation and showed no anti-myeloma effects. Twenty-eight days following implantation of LAGλ–1 tumor, mice received ATO (1.25 mg/kg) or melphalan (0.6 mg/kg) alone at doses without anti-myeloma effects, or the combination of these agents at these doses. The animals treated with these drugs alone showed a similar growth and increase in paraprotein levels to control mice whereas the combination of ATO and melphalan at these low doses markedly suppressed the growth of the tumor by >50% and significantly reduced serum paraprotein levels. These in vitro and in vivo studies suggest that the addition of ATO to other anti-myeloma agents is likely to result in improved outcomes for patients with drug resistant myeloma. Based on these results, these combinations are now in clinical trials with promising early results for patients with drug resistant myeloma.

Combined Fludarabine, Cyclophosphamide, and Alemtuzumab (FCC), an Active Regimen for Treated Patients with Chronic Lymphocytic Leukemia (CLL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3133-3133 ◽  
Author(s):  
Marco Montillo ◽  
Sara Miqueleiz ◽  
Alessandra Tedeschi ◽  
Francesca Ricci ◽  
Eleonora Vismara ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Residual Disease ◽  
Single Agent ◽  
Lymphocytic Leukemia ◽  
Combination Regimen ◽  
Synergistic Activity ◽  
Color Flow ◽  
Grade Iii

Abstract Fludarabine (F) in combination with cyclophosphamide (C) showed a relevant advantage over single-agent F in pts with relapsed CLL. Although minimal residual disease (MRD) remains detectable in many pts achieving CR, the combination of F and C seems to reduce MRD more efficiently. Still, pts in CR eventually relapse and require treatment, demonstrating the need for improved treatments able to further reduce or eliminate MRD and induce “better quality” and thus more durable responses. Alemtuzumab (CAM), anti-CD52 monoclonal antibody, acts synergistically with F in vitro and appears to have synergistic activity in vivo. Additionally, CAM is highly effective at clearing disease from bone marrow, the usual site of residual disease following purine analogue-based treatment. Therefore, we designed a phase II study to determine feasibility and efficacy, overall response rate (ORR)-duration of response-ability at clearing MRD, of a 4-weekly combination regimen consisting of F, C, and CAM (FCC). The study population is represented by pts with B-CLL with relapsed or refractory disease after at least one line of treatment. Subcutaneous route of administration of CAM has been adopted in this trial. MRD was measured by 4-color flow cytometry in the bone marrow. The FCC regimen consisted of F 40 mg/m2/d os (d 1–3), C 250 mg/m2/d os (d 1–3) and CAM 10 mg sc (d 1–3). This combination was repeated on d 29 for up to 6 cycles. The dose of CAM was increased after the first cohort of 10 treated pts from 10 mg to 20 mg sc. Currently, 25 pts have been enrolled in this trial. Median age was 57 years (range 42–79), 15/25 (60%) were male, 23/25 (92%) were in Binet stage B or C, median number of prior treatment regimens was 2 (range 1–4). In six (24%) pts 17p deletion was detected. IgVH unmutated was observed in 17 (68%) pts. At the moment of writing 19 pts are eligible for evaluation of toxicity and response. The ORR was 79%, with 7 (37%) pts achieving CR, 7 (37%) pts a PR, 1 (5%) pt a PRn. Three pts had SD, while 1 showed progression of the disease. MRD negativity was achieved in the bone marrow of 4/15 (27%) pts. Grade III-IV neutropenia episodes were observed in 43% of the administered courses while grade III-IV thrombocytopenia episodes were detected only in 8% of cycles. Four major infections were recorded: two sustained by Mycobacterium tuberculosis (1 cutis, 1 lung), one by Nocardia (lung) and one by E. coli (sepsis). The patient with pneumonia due to M. tuberculosis died because of respiratory failure. CMV reactivation occurred in 6 pts: no CMV disease was recorded. After a median follow up of 10 m (range 1–22) 73% of responding pts did not progressed. In conclusion, results from the interim analysis of this new, 4-weekly dosing FCC regimen suggest that combination therapy with F, C and CAM is feasible, safe, and effective in treating pts with relapsed and refractory CLL, even in those patients with inherent poor prognostic factors and who had received.

scholarly journals In Vitro Interactions of Echinocandins with Triazoles Against Multidrug-Resistant Candida auris

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S82-S82
Author(s):  
Hamid Badalii
Keyword(s):  
Amphotericin B ◽  
Antifungal Susceptibility ◽  
Multidrug Resistant ◽  
In Vivo Studies ◽  
Synergistic Activity ◽  
Candida Auris ◽  
Unsuccessful Treatment ◽  
In Vitro Interactions

Abstract Background Blood stream infections due to Candida auris are related to a high mortality rate and treatment failure attributed to resistance to fluconazole, voriconazole, amphotericin B, and caspofungin. Thus, the precise identification of agents and in vitro antifungal susceptibility testing is highly recommended. Novel therapeutic strategies, such as combination therapy, are essential for increasing the efficacy and reducing the toxicity of antifungal agents. Therefore, we investigated the in vitro combination of micafungin plus voriconazole against multidrug-resistant C. auris isolated from cases of candidemia. Methods The in vitro interactions between echinocandins and azoles were determined against ten multidrug-resistant Candida auris strains by using a microdilution checkerboard technique. Results Results revealed that MICs range for voriconazole and micafungin were 0.5–8 and 0.25–8 mg/l, respectively. The checkerboard analysis revealed that the combination of micafungin with voriconazole exhibited synergistic activity against all 10 multidrug-resistant C. auris isolates (FICI range: 0.15–0.5). Overall, no antagonistic effects were observed in this experiments. Conclusion In vitro studies have previously suggested that among azoles isavuconazole and posaconazole are more active drugs against C. auris. In addition, the majority of isolates reported are resistant to fluconazole. Remarkably, unsuccessful treatment of C. auris infections with fluconazole, voriconazole, amphotericin B, caspofungin, and anidulafungin has been already on record. Here in we demonstrates that interaction between micafungin with voriconazole exhibited synergistic activity against multidrug-resistant C. auris isolates. It seems that lower concentrations of drugs cause fewer side-effects and improve the treatment outcomes. However, in vivo studies with suitable animal models of C. auris infection is highly recommended. Disclosures All authors: No reported disclosures.

scholarly journals Combination of Colistin and Azidothymidine Demonstrates Synergistic Activity against Colistin-Resistant, Carbapenem-Resistant Klebsiella pneumoniae

2020 ◽  
Vol 8 (12) ◽  
pp. 1964
Author(s):  
Ya-Ting Chang ◽  
Tsung-Ying Yang ◽  
Po-Liang Lu ◽  
Shang-Yi Lin ◽  
Liang-Chun Wang ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Therapeutic Option ◽  
Rapid Evolution ◽  
Toxicity Testing ◽  
World Health ◽  
Synergistic Activity ◽  
Carbapenem Resistant

Carbapenem-resistant Enterobacteriaceae (CRE) is listed as an urgent threat by the World Health Organization because of the limited therapeutic options, rapid evolution of resistance mechanisms, and worldwide dissemination. Colistin is a common backbone agent among the “last-resort” antibiotics for CRE; however, its emerging resistance among CRE has taken the present dilemma to the next level. Azidothymidine (AZT), a thymidine analog used to treat human immunodeficiency virus/acquired immunodeficiency syndrome, has been known to possess antibacterial effects against Enterobacteriaceae. In this study, we investigated the combined effects of AZT and colistin in 40 clinical isolates of colistin-resistant, carbapenem-resistant K. pneumoniae (CCRKP). Eleven of the 40 isolates harbored Klebsiella pneumoniae carbapenemase. The in vitro checkerboard method and in vivo nematode killing assay both revealed synergistic activity between the two agents, with fractional inhibitory concentration indexes of ≤0.5 in every strain. Additionally, a significantly lower hazard ratio was observed for the nematodes treated with combination therapy (0.288; p < 0.0001) compared with either AZT or colistin treatment. Toxicity testing indicated potentially low toxicity of the combination therapy. Thus, the AZT–colistin combination could be a potentially favorable therapeutic option for treating CCRKP.

scholarly journals In Vivo and In Vitro Pharmacodynamics of Anthelmintic Medication Used in Sheep

2019 ◽  
Vol 76 (2) ◽  
pp. 175
Author(s):  
Mihai CERNEA ◽  
Roxana FILIP ◽  
Raul CĂTANĂ ◽  
Laura CĂTANĂ
Keyword(s):  
Anthelmintic Resistance ◽  
In Vivo Studies ◽  
In Vitro Tests ◽  
Minimal Risk ◽  
Egg Hatch ◽  
Superior Efficacy ◽  
Reference Concentration ◽  
Post Therapy

Our research aimed to evaluate the efficacy of anthelmintic treatments in sheep, as well as the resistance occurrence risk for the most commonly used substances. Anthelmintic medication efficacy was evaluated on 30 animals from a private farm, located in Sânmihaiu Almaşului, Sălaj County. In vivo studies were performed by using Fecal Egg Count Reduction Test (FECRT) and testing an albendazole-based (ABZ) product. In vitro, we used Egg Hatch Assay (EHA) and Larval Development Assay (LDA) for albendazole (ABZ), mebendazole (MBZ), fenbendazole (FBZ), thiabendazole (TBZ) and ivermectin (IVM) (only for LDA). FECRT showed that intestinal nematodes developed resistance phenomena against the ABZ-based product, with an extensivity of 80% at seven days post therapy, an egg reduction percentage of 41.89% at seven days post-therapy and 43.9% at 14 days post-therapy. The in vitro EHA highlighted a superior efficacy of TBZ (egg hatch percentage at reference concentration being 51.21) compared to ABZ (71.89%), MBZ (84.46%) and FBZ (79.22%), with a minimum risk of anthelmintic resistance. The LDA test revealed the superior efficacy of FBZ (MIC 0.59 mcg/ml) and IVM (MIC 0.078 mcg/ml), with a minimal risk of inducing parasitic resistance. All in vivo and in vitro tests revealed a limited ABZ efficacy, recommending avoiding the therapy with this substance.

scholarly journals Antimicrobial Activity from Species Plectranthus amboinicus (Lour.) Spreng, a Review

2020 ◽  
pp. 1-14
Author(s):  
Juliane Maria dos Santos Silva ◽  
Jackson Roberto Guedes da Silva Almeida ◽  
Cristiane dos Santos Cerqueira Alves ◽  
Daniel Amando Nery ◽  
Livia Maria Oliveira Damasceno ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Synergistic Activity ◽  
Popular Medicine ◽  
Plectranthus Amboinicus

Introduction: Nowadays, several bacteria have acquired resistance to available antimicrobial agents making necessary the search for new therapeutic alternatives. Plectranthus amboinicus L. is a succulent and aromatic herb, popularly known as thick leaf mint, used in popular medicine for the treatment of colds, digestive diseases, asthma, headache and to fight pathogenic bacteria activity. In view the antimicrobial activity of P. amboinicus this study had as aim to review publications involving researches about antimicrobial activity of this species. Materials and Methods: For this, PubMed, Scopus, Science Direct and Scielo databases were consulted in November 2020 using the keywords Plectranthus amboinicus and antimicrobial activity. In vitro and/or in vivo studies on the antimicrobial activity of the species in the last 10 years were considered. Results: The main microorganisms evaluated were: Klebsiella pneumoniae, Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and some Candida species. The essential oils had carvacrol, germacrene D, thymol and camphor as main constituents. Most studies evaluated the antimicrobial activity using broth dilution and agar diffusion methods. In most studies essential oil, extracts and/or isolated substances showed significant antimicrobial activity. Synergistic activity was also observed through association with antibiotics. Conclusion: P. amboinicus has therapeutic potential for antimicrobial treatments and can be an alternative to the treatment of resistant microorganisms and that further in vivo and clinical studies with the species are still needed.

Sildenafil in combination therapy against cancer: A literature review

2020 ◽  
Vol 27 ◽  
Author(s):  
Rabah Iratni ◽  
Mohammed Akli Ayoub
Keyword(s):  
Combination Therapy ◽  
Drug Repurposing ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
Beneficial Effects ◽  
Chemotherapy Drugs ◽  
Anti Cancer ◽  
Hypertensive Drug

: The concept of drug repurposing and Sildenafil or blue pill are tightly linked over the years. Indeed, in addition to its initial clinical application as an anti-hypertensive drug in the pulmonary system, Sildenafil is also known for its beneficial effects in erectile dysfunction. Moreover, evidence have been accumulated to support its value in anti-cancer therapy either alone or in a combination with other clinically efficient chemotherapy drugs. In this review, we focused on the old and recent in vitro and in vivo studies demonstrating the cellular and molecular rationale for the application of Sildenafil in combination therapy in many various types of cancer. We emphasized on the different molecular targets as well as the different signaling pathways involved in cancer cells. The pro-apoptotic effect of Sildenafil through nitric oxide (NO)/ phosphodiesterase type 5 (PDE5)-dependent manner seems to be one of the most common mechanisms. However, the activation of autophagy as well as the modulation of the anti-tumor immunity constitute the other pathways triggered by Sildenafil. Overall, the studies converged to reveal the complexity of the anti-cancer potential of Sildenafil. Thus, through our review we aimed to present an updated and simplified picture of such repurposing of Sildenafil in the field of oncology.

scholarly journals Honokiol Restores Polymyxin Susceptibility to MCR-1-Positive Pathogens both In Vitro and In Vivo

2019 ◽  
Vol 86 (5) ◽  
Author(s):  
Yan Guo ◽  
Xiaohong Lv ◽  
Yanling Wang ◽  
Yonglin Zhou ◽  
Na Lu ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Molecular Simulation ◽  
Natural Compound ◽  
Combined Therapy ◽  
Bacterial Load ◽  
Promising Alternative ◽  
Content Type ◽  
Time Kill

ABSTRACT The emergence of the plasmid-mediated colistin resistance gene mcr-1 has led to serious multidrug-resistant (MDR) Enterobacteriaceae infections, which are a great threat to the clinic. This study aims to find an inhibitor of MCR-1 to reestablish the use of polymyxins against MDR Enterobacteriaceae infections. Here, we determined that the natural compound honokiol could enhance the efficacy of polymyxins against MDR Enterobacteriaceae infections by a checkerboard MIC assay, a time-kill assay, a combined disk test, Western blotting, molecular simulation dynamics, and mouse infection models. The MIC results indicated that honokiol can recover the sensitivity of polymyxins against MCR-1-positive Klebsiella pneumoniae and Escherichia coli (with a fractional inhibitory concentration index ranging from 0.09 ± 0.00 to 0.27 ± 0.06). Based on time-kill curve analysis, all of the tested bacteria were killed within 1 h following the combined therapy with honokiol and polymyxins. Molecular simulation dynamics results suggested that honokiol directly binds to the MCR-1 active region, reducing the biological activity of MCR-1. The combination of honokiol and polymyxins could increase the 40% protection rate and reduce the bacterial load on the thigh muscles of mice. Our study indicates that honokiol is a predominant natural compound whose combination therapy with polymyxins is very promising in future treatment options for MCR-1-positive Enterobacteriaceae infections. IMPORTANCE In the present study, honokiol could effectively inhibit the activity of MCR-1 and showed almost no cytotoxicity to MH-S cells. According to our results, the combination of honokiol and polymyxin had a clear synergistic effect against MCR-1-positive Enterobacteriaceae in vitro. Combination therapy also showed a powerful therapeutic effect in vivo, which can significantly improve mouse livability, reduced the load of bacteria, and reduced pathological change. This combined therapy of small molecule compounds and antibiotics may not continue to induce new bacterial resistance, due to the fact that MCR-1 targeted by honokiol is not indispensable for the bacterial viability; on the other hand, it can reduce the dosage of combined antibiotics, and it is also a promising alternative therapy for the treatment of drug-resistant infections in the future.

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