Study of an antifungal medicine isavuconazole used in treatment of mold infections in China: A plain language summary.

WHAT IS THIS SUMMARY ABOUT?: Molds are types of fungus that can cause sickness and death. Mold infections are increasing in China. Until 2022, medicines that can effectively treat all mold infections were still lacking in China. This summary of a study originally published in the journal Infection and Drug Resistance. The study took place in China and tested a medicine called isavuconazole on mold samples to check if isavuconazole can be used to treat mold infections. Isavuconazole became available in China in January 2022 as a capsule (a hard gel-covered pill filled with a dose of medicine) and in June 2022 as an injection or a shot. WHAT WERE THE RESULTS?: Isavuconazole stopped the growth of most molds. Other medicines were needed at higher amounts to stop the growth of molds. WHAT DO THE RESULTS OF THE STUDY MEAN?: Isavuconazole is another option to treat mold infections in China.

Global update on the in vitro activity of tigecycline and comparators against isolates of Acinetobacter baumannii and rates of resistant phenotypes (2016-2018).

OBJECTIVES: This study presents 2016-2018 in vitro antimicrobial activity data and rates of resistant phenotypes for clinical isolates of Acinetobacter baumannii from Africa/Middle East, Asia/South Pacific, Europe, Latin America, and North America. METHODS: A total of 4320 A. baumannii isolates were collected across all regions between 2016 and 2018. The in vitro antimicrobial activities of amikacin, colistin, levofloxacin, meropenem, and tigecycline were determined using the broth microdilution methodology of the Clinical and Laboratory Standards Institute. MICs were interpreted using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (version 11.0). Rates of subsets that were resistant to amikacin, colistin, levofloxacin, and meropenem, according to EUCAST breakpoints, are also presented. RESULTS: In each region, tigecycline and colistin were active against isolates of A. baumannii (MIC90 values, 1 or 2 mg/L) and the lowest rate of resistance was to colistin (1.2%-7.3%). The rates of resistance to the panel of agents were generally lower among A. baumannii from North America (1.3%-42.7%), compared with the other regions. Fewer than 11% of meropenem-resistant A. baumannii were also resistant to colistin. The rates of amikacin-, levofloxacin- and meropenem-resistant A. baumannii were lowest in North America and mostly higher in Africa/Middle East and Latin America. CONCLUSION: In each geographical region, tigecycline and colistin maintained good in vitro antimicrobial activity against isolates of A. baumannii, including antimicrobial-resistant subsets. The higher rates of meropenem-resistant isolates, particularly in Africa/Middle East and Latin America, require continued monitoring because of the scarcity of effective treatment options.

In vitro Activity of Isavuconazole and Comparators Against Clinical Isolates of Molds from a Multicenter Study in China.

Purpose: Monitoring antifungal susceptibility patterns for new or established antifungals is imperative. Antifungal resistance is frequent in molds, frequently leading to invasive mold infections (IMIs) in immunocompromised patients with high morbidity and mortality. Limited availability of effective antifungals for treatment of IMIs in China is an enormous challenge. The purpose of this study was to monitor in vitro antifungal resistance profiles of mold isolates from China, with a particular focus on evaluating in vitro isavuconazole (ISA) activity against these isolates, contributing to the treatment guidance in clinics. Methods: We evaluated the in vitro activity of ISA and its comparators (voriconazole [VOR] and amphotericin B [AMB]) against 131 clinical isolates of Aspergillus spp. (n = 105) and Mucorales order (n = 26) collected between 2017 and 2020 from China. Results: ISA and VOR exhibited similar in vitro activity against Aspergillus spp., with minimum inhibitory concentration (MIC)50 of 1 µg/mL and MIC90 of 2 µg/mL, respectively. Overall, AMB was less active than azoles against Aspergillus spp. (MIC50: 4 µg/mL, MIC90: 8 µg/mL). Against the Mucorales order, ISA demonstrated MIC50 of 0.5 µg/mL and MIC90 of 1 µg/mL; however, one strain each of Mucor circinelloides and Syncephalastrum racemosum were resistant to ISA (MICs: >8 µg/mL). VOR exhibited little or no activity (MIC50: 8 µg/mL, MIC90: >8 µg/mL) against the Mucorales order, whereas AMB had MIC50 and MIC90 of 1 µg/mL. Conclusion: This was the first multicenter, in vitro study conducted in China and demonstrated the excellent activities of ISA against most species of the Mucorales order. MIC indicated an advantage over currently available azole antifungals, positioning ISA as a potential alternative to VOR for clinical management of IMIs. As with other antimicrobials, clinicians should employ stewardship and best practices in relation to potential resistance to new azole antifungals.

Antifungal drugs work together to treat germs causing fungal infections.

Life-threatening infections can be caused by a fungus called Candida auris (shortened to C. auris) that is found in the hospital environment. This study looked at how well different drugs could treat C. auris infection. Samples were collected from 36 people who had C. auris infection. The samples were treated with single drugs and in combination. We found that the main drug types did not work on most samples. Genetic differences we found in the C. auris samples could explain why the main drugs did not work. However, a drug called isavuconazole worked on almost all samples. We also found that a drug called anidulafungin worked better against C. auris when it was combined with either isavuconazole or another drug called voriconazole. To read the full Plain Language Summary of this article, click on the View Article button above and download the PDF.

Evaluation of Synergistic Activity of Isavuconazole or Voriconazole plus Anidulafungin and the Occurrence and Genetic Characterization of Candida auris Detected in a Surveillance Program.

A total of 15 Candida auris isolates from the SENTRY antimicrobial surveillance program between 2006 and 2019 were combined with 21 isolates from other collections for the evaluation of antifungal susceptibility and synergy against anidulafungin plus voriconazole or isavuconazole using the checkerboard method. Surveillance isolates were analyzed for genetic relatedness and resistance mechanisms. Applying the tentative statistical epidemiological cutoff values and the Centers for Disease Control tentative breakpoints, 32/36 isolates were resistant to fluconazole, 5/36 were resistant to amphotericin B, 5/36 were non-wild-type (NWT) to anidulafungin, 3/36 were NWT to micafungin, and 1/36 and 10/36 were NWT to isavuconazole and voriconazole, respectively. Of these, 10 isolates were multidrug resistant, which means that these isolates were resistant to 2 antifungal classes. Synergy or partial synergy was noted in 5/36 and 22/36, respectively, of the isolates with the combination of anidulafungin plus voriconazole, and 11/36 and 19/36 isolates, respectively, for the combination of anidulafungin plus isavuconazole. Multilocus sequence type (MLST) analysis of the 15 SENTRY isolates demonstrated that the isolates from the US were genetically related to, but different from, isolates from Latin America (Panama and Colombia) and Germany. Single nucleotide polymorphism (SNP) analysis showed that the 15 SENTRY isolates belonged to the described international clades and had associated Erg11 alterations, including 11 isolates displaying K143R, one displaying F126L, and one displaying Y501H alterations and a fluconazole MIC result of ≥64 mg/liter. Resistance mechanisms were not observed in the two isolates displaying fluconazole MIC values at 4 and 16 mg/liter. Isavuconazole displayed activity and greater synergy when tested with anidulafungin than seen with anidulafungin plus voriconazole against the C. auris clinical isolates that displayed resistance phenotypes.

A current and historical perspective on disparities in US childhood pneumococcal conjugate vaccine adherence and in rates of invasive pneumococcal disease: Considerations for the routinely-recommended, pediatric PCV dosing schedule in the United States.

Previous research has suggested that reducing the US 4-dose PCV13 schedule to a 3-dose schedule may provide cost savings, despite more childhood pneumococcal disease. The study also stressed that dose reduction should be coupled with improved PCV adherence, however, US PCV uptake has leveled-off since 2008. An estimated 24-36% of US children aged 5-19 months are already receiving a reduced PCV schedule (i.e., missing ≥1 dose). This raises a practical concern that, under a reduced, 3-dose schedule, a similar proportion of children may receive ≤2 doses. It is also unknown if a reduced, 3-dose PCV schedule in the United States will afford the same disease protection as 3-dose schedules used elsewhere, given lower US PCV adherence. Finally, more assurance is needed that, under a reduced schedule, racial, socioeconomic, and geographic disparities in PCV adherence will not correspond with disproportionately higher rates of pneumococcal disease among poor or minority children.