synergy
SusceptibilityAssessment of Piperacillin-Tazobactam-Meropenem Synergy against Serine Carbapenemase-Producing Enterobacterales Using Time-Kill AssaysSynergy between piperacillin-tazobactam and meropenem against KPC-producing Klebsiella pneumoniae was recently demonstrated. We sought to test the combination against a broader range of serine carbapenemase producers.
Antiviral AgentsInhibition of Arenaviruses by Combinations of Orally Available Approved DrugsNeglected diseases caused by arenaviruses such as Lassa virus (LASV) and filoviruses like Ebola virus (EBOV) primarily afflict resource-limited countries, where antiviral drug development is often minimal. Previous studies have shown that many approved drugs developed for other clinical indications inhibit EBOV and LASV and that combinations of these drugs provide synergistic suppression of EBOV, often by blocking discrete steps in...
Experimental Therapeuticsβ-Lactam Combinations That Exhibit Synergy against Mycobacteroides abscessus Clinical IsolatesMycobacteroides abscessus (Mab) is an opportunistic environmental pathogen that can cause chronic pulmonary disease in the setting of structural lung conditions such as bronchiectasis, chronic obstructive pulmonary disease, and cystic fibrosis. These infections are often incurable and associated with rapid lung function decline. Mab is naturally...
PharmacologyArtemisinin-Based Drugs Target the Plasmodium falciparum Heme Detoxification PathwayArtemisinin (ART)-based antimalarial drugs are believed to exert lethal effects on malarial parasites by alkylating a variety of intracellular molecular targets. Recent work with live parasites has shown that one of the alkylated targets is free heme within the parasite digestive vacuole, which is liberated upon hemoglobin catabolism by the intraerythrocytic parasite, and that reduced levels of heme alkylation occur in artemisinin-...
Experimental TherapeuticsDeimmunized Lysostaphin Synergizes with Small-Molecule Chemotherapies and Resensitizes Methicillin-Resistant Staphylococcus aureus to β-Lactam AntibioticsThere is an urgent need for novel agents to treat drug-resistant bacterial infections, such as multidrug-resistant Staphylococcus aureus (MRSA). Desirable properties for new antibiotics include high potency, narrow species selectivity, low propensity to elicit new resistance phenotypes, and synergy with standard-of-care (SOC) chemotherapies.
Mechanisms of ResistanceBurkholderia ubonensis High-Level Tetracycline Resistance Is Due to Efflux Pump Synergy Involving a Novel TetA(64) Resistance DeterminantBurkholderia ubonensis, a nonpathogenic soil bacterium belonging to the Burkholderia cepacia complex (Bcc), is highly resistant to some clinically significant antibiotics. The concern is that B. ubonensis may serve as a resistance reservoir for Bcc or...
Experimental TherapeuticsImipenem/Cilastatin/Relebactam Alone and in Combination against Pseudomonas aeruginosa in the In Vitro Pharmacodynamic ModelCombination therapy may enhance imipenem/cilastatin/relebactam’s (I/R) activity against Pseudomonas aeruginosa and suppress resistance development. Human-simulated unbound plasma concentrations of I/R at 1.25 g every 6 h (h), colistin at 360 mg daily, and amikacin at 25 mg/kg daily were reproduced alone and in combination against six imipenem-nonsusceptible...
SusceptibilityAntifungal Susceptibility Profiles and Drug Resistance Mechanisms of Clinical Lomentospora prolificans IsolatesLomentospora prolificans is an opportunistic fungal pathogen with low susceptibility to current antifungal drugs. Here, we tested the in vitro susceptibility of 8 drugs against 42 clinical L. prolificans isolates. All isolates showed high MICs to voriconazole (MIC90>16 μg/ml...
Experimental TherapeuticsActivity of Cefiderocol Alone and in Combination with Levofloxacin, Minocycline, Polymyxin B, or Trimethoprim-Sulfamethoxazole against Multidrug-Resistant Stenotrophomonas maltophiliaThe production of an L1 metallo-β-lactamase and an L2 serine active-site β-lactamase precludes the use of β-lactams for the treatment of Stenotrophomonas maltophilia infections. Preclinical data suggest that cefiderocol is the first approved β-lactam with reliable activity against S. maltophilia,...
Experimental TherapeuticsRepurposing the Antiamoebic Drug Diiodohydroxyquinoline for Treatment of Clostridioides difficile InfectionsClostridioides difficile, the leading cause of nosocomial infections, is an urgent health threat worldwide. The increased incidence and severity of disease, the high recurrence rates, and the dearth of effective anticlostridial drugs have created an urgent need for new therapeutic agents. In an effort to discover new drugs for the treatment of...