A total of 15
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
clinical isolates that displayed resistance phenotypes.
: 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.
: A total of 4,320 A. baumannii isolates were collected from 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. Minimum inhibitory concentrations (MICs) were interpreted using the European Committee on Antimicrobial Susceptibility Testing breakpoints (version 11.0). Rates of subsets that were resistant to amikacin, colistin, levofloxacin and meropenem, according to EUCAST breakpoints, are also presented.
: 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.
: 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 due to the scarcity of effective treatment options. 249/250 words
Oxacillinases (OXA)-48-like β-lactamases are one of the most common resistance determinants among carbapenem-resistant Enterobacterales reported globally. Moreover, there is no standard treatment ...available against organisms producing OXA-48-like enzymes, and they are sometimes difficult to detect, making treatment challenging. The objective of this study was to evaluate the distribution and antimicrobial susceptibility of
Enterobacterales isolates against ceftazidime-avibactam (CAZ-AVI) and a panel of comparators collected worldwide from 2016 to 2020 as a part of the Antimicrobial Testing Leadership and Surveillance program. Among all the Enterobacterales isolates collected, 1.8% (1,690/94,052) carried
and a majority of those were identified as
(86.5%, 1,462/1,690). Among all the
isolates, 88.9% (1,502/1,690) were extended-spectrum β-lactamase (ESBL)-positive, 20.7% (350/1,690) were metallo-β-lactamase (MBL)-positive, and 8.9% (150/1,690) were ESBL- and MBL-negative. There were 10 different variants of the OXA-48-like family of enzymes detected, with the major variant being
(50.2%, 848/1,690),
(29.3%, 496/1,690), and
(18.0%, 304/1,690). Overall, all the
isolates showed a susceptibility of 78.6% to CAZ-AVI. Importantly, high susceptibility to CAZ-AVI was shown by all the
type, MBL-negative isolates (
= 1,380, ≥99.0%), and all the MBL-negative isolates (
= 1,300, ≥97.6%) of the major variants (
, and
) studied. Among the comparator agents, all isolates showed good susceptibility to only tigecycline (>95.0%) and colistin (>78.6%). Considering the limited treatment options available, CAZ-AVI could be considered as a potential treatment option against
Enterobacterales. However, routine surveillance and appropriate stewardship strategies for these organisms may help identify emerging resistance mechanisms and effective treatment of infections.
Resistance to carbapenems among Enterobacterales is often due to the production of enzymes that are members of the oxacillinases (OXA)-48-like family. These organisms can also be resistant to other classes of drugs and are difficult to identify and treat. This study evaluated the activity of the drug ceftazidime-avibactam (CAZ-AVI) and other comparator agents against a global collection of Enterobacterales that produce OXA-48-like enzymes. CAZ-AVI was active against
Enterobacterales, and only colistin and tigecycline were similarly active among the comparator agents, highlighting the limited treatment options against these organisms. Continued surveillance of the distribution of these OXA 48-like producing Enterobacterales and monitoring of resistance patterns along with the implementation of antimicrobial stewardship measures to guide antibiotic use and appropriate treatment are necessary to avoid drug resistance among these organisms.
•Of all the P. aeruginosa isolates, 20.9% were MDR and 20.7% were XDR.•Latin America had the highest proportion of all resistant isolates.•Overall, P. aeruginosa isolates showed high susceptibility ...(90.9%) to CAZ-AVI.•MDR (59.6%) and XDR isolates (60.7%) had lower susceptibility to CAZ-AVI.•Only colistin showed high susceptibility (>98.3%) across all P. aeruginosa isolates.
The objective of this study was to assess the distribution and antimicrobial susceptibility of Pseudomonas aeruginosa isolates against ceftazidime-avibactam (CAZ-AVI) and a panel of comparator agents collected globally and in each region from 2017–2020 from the Antimicrobial Testing Leadership and Surveillance program.
Susceptibility and minimum inhibitory concentration of all P. aeruginosa isolates were determined using broth microdilution methodology according to the Clinical and Laboratory Standards Institute guidelines.
Of the total 29746 isolates of P. aeruginosa collected, 20.9% were multidrug resistant (MDR), 20.7% were extremely drug resistant (XDR), 8.4% were CAZ-AVI-resistant (CAZ-AVI-R), and 3.0% were MBL-positive. Amongst the MBL-positive isolates, the proportion of VIM-positive isolates was highest (77.8%). The highest proportion of MDR (25.5%), XDR (25.0%), MBL-positive (5.7%), and CAZ-AVI-R (12.3%) isolates were in Latin America. Amongst the sources, the highest proportion of isolates were from respiratory sources (43.0%), and the majority of isolates were from non-intensive care unit wards (71.2%). Overall, all P. aeruginosa isolates (90.9%) showed high susceptibility to CAZ-AVI. However, MDR and XDR isolates were less susceptible to CAZ-AVI (≤60.7). The only comparators to which all isolates of P. aeruginosa showed good overall susceptibility were colistin (99.1%) and amikacin (90.5%). However, only colistin was active (≥98.3%) against all the resistant isolates.
CAZ-AVI presents a potential treatment option against P. aeruginosa infections. However, active monitoring and surveillance, especially of the resistant phenotypes, is warranted for effective treatment of infections caused by P. aeruginosa.
•Ceftaroline is a key therapeutic option for community-acquired pneumonia (CAP).•≥99.95% MSSA and ≥78.07% MRSA isolates were ceftaroline-susceptible.•For MRSA, susceptibility to ceftaroline was ...highest in 0–18 years (92.74%).•≥99.74% PISP and ≥86.23% of PRSP isolates were susceptible to ceftaroline.•≥93.02% βL-neg and ≥77.78% βL-pos H. influenzae were susceptible to ceftaroline.
Ceftaroline is an important therapeutic option for community-acquired pneumonia (CAP). Antimicrobial susceptibility to ceftaroline and other antimicrobial agents against Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae isolates collected worldwide from identified respiratory tract sources is reported by age groups (0–18, 19–65, and >65 years).
Antimicrobial susceptibility of isolates, collected as part of the ATLAS program (2017–2019), was performed per EUCAST/CLSI guidelines.
S. aureus (N = 7103; methicillin-susceptible S. aureus MSSA = 4203; methicillin-resistant S. aureus MRSA = 2791), S. pneumoniae (N = 4823; EUCAST/CLSI, penicillin-intermediate S. pneumoniae PISP = 1408/870; penicillin-resistant S. pneumoniae PRSP = 455/993), and H. influenzae (N = 3850; β-lactamase βL-negative = 3097; βL-positive = 753) isolates were collected from respiratory tract specimens. Susceptibility to ceftaroline was 89.08%–97.83% for S. aureus, 99.95%–100% for MSSA, and 78.07%–92.74% for MRSA isolates across age groups; S. aureus as well as MRSA isolates derived from the 0–18 years age group demonstrated the highest susceptibility rates to ceftaroline. Susceptibility to ceftaroline was 98.25%–99.77% for S. pneumoniae, 99.74%–100% for PISP, and 86.23%–99.04% for PRSP isolates across age groups. Across all age groups, susceptibility to ceftaroline was 89.53%–99.70% for H. influenzae, 93.02%–100% for βL-negative, and 77.78%–98.35% for βL-positive isolates.
Irrespective of age, susceptibility to ceftaroline was high among the majority of S. aureus, S. pneumoniae, and H. influenzae isolates collected in this study.
The objective of this study was to assess the in vitro activity of ceftaroline and a panel of comparator agents against isolates causing skin and soft tissue infections (SSTIs) collected in ...Africa/Middle East, Asia–Pacific, Europe, and Latin America from 2019–2020. Minimum inhibitory concentrations (MIC) were determined using European Committee on Antimicrobial Susceptibility Testing criteria. All the methicillin-susceptible Staphylococcus aureus (MSSA) isolates were susceptible to ceftaroline. Across all regions, ceftaroline demonstrated potent activity against methicillin-resistant S. aureus (MRSA, susceptibility 89.5–93.7%) isolates. Susceptibility to vancomycin, daptomycin, linezolid, teicoplanin, trimethoprim sulfamethoxazole, and tigecycline was ≥94.1% in MSSA and MRSA isolates. Against β-hemolytic streptococci isolates, ceftaroline demonstrated very potent activity (MIC90 0.008–0.03 mg/L) across all regions. All β-hemolytic streptococci isolates were susceptible to linezolid, penicillin, and vancomycin (MIC90 0.06–2 mg/L). Among the extended-spectrum β-lactamases (ESBL)-negative Enterobacterales tested (E. coli, K. pneumoniae, and K. oxytoca), susceptibility to ceftaroline was high (88.2–98.6%) in all regions. All ESBL-negative Enterobacterales were susceptible to aztreonam. Potent activity was observed for amikacin, cefepime, and meropenem (94.1–100%) against these isolates. Overall, ceftaroline showed potent in vitro activity against isolates of pathogens causing SSTIs. Continuous surveillance of global and regional susceptibility patterns is needed to guide appropriate treatment options against these pathogens.
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
. 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.
Isavuconazole stopped the growth of most molds. Other medicines were needed at higher amounts to stop the growth of molds.
Isavuconazole is another option to treat mold infections in China.
•Gram-negative respiratory isolates showed high susceptibility (>91%) to CAZ-AVI.•Except P. aeruginosa, MDR isolates showed >88% susceptibility to CAZ-AVI.•Prevalence of XDR P. aeruginosa and XDR K. ...pneumoniae was high (>22%).•Only colistin showed high susceptibility across all the organisms (>81%).
The objective of this study was to assess the in vitro activity of ceftazidime-avibactam (CAZ-AVI) and a panel of comparator agents against isolates of Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa collected in 2018 and 2019 by different centres worldwide from patients with respiratory tract infections.
Susceptibility and minimum inhibitory concentration (MIC) of all organisms were determined using broth microdilution methodology for CAZ-AVI, and a panel of comparator antimicrobial agents by a central reference laboratory according to Clinical and Laboratory Standards Institute guidelines and European Committee on Antimicrobial Susceptibility Testing guidelines.
CAZ-AVI demonstrated potent antimicrobial activity against isolates of Enterobacter spp. (97.6% susceptibility, MIC90, 1 µg/ml), E. coli (98.5% susceptibility, MIC90, 0.25 µg/ml), K. pneumoniae (94.7% susceptibility, MIC90 2 µg/ml), and P. aeruginosa (91.2% susceptibility, MIC90 8 µg/ml). CAZ-AVI was also active (susceptibility >85%) against MDR isolates for all organisms except P. aeruginosa. Only a small proportion (<10%) of all isolates of Enterobacter spp. and E. coli were identified as XDR compared to isolates of K. pneumoniae and P. aeruginosa isolates (>20%). Susceptibility to CAZ-AVI was high (>70%) among XDR isolates of Enterobacter spp., K. pneumoniae, and E. coli, compared to P. aeruginosa (<70%). Among the comparator agents, only colistin showed consistent activity across all the organisms (>85%).
Gram-negative respiratory isolates collected in 2018–2019 showed high susceptibility to CAZ-AVI; CAZ-AVI represents a potential treatment option against infection caused by these organisms.
Life-threatening infections can be caused by a fungus called
(shortened to
) that is found in the hospital environment. This study looked at how well different drugs could treat
infection. Samples ...were collected from 36 people who had
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
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
when it was combined with either isavuconazole or another drug called voriconazole.
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.
We evaluated the in vitro activity of ISA and its comparators (voriconazole VOR and amphotericin B AMB) against 131 clinical isolates of
spp. (
= 105) and
order (
= 26) collected between 2017 and 2020 from China.
ISA and VOR exhibited similar in vitro activity against
spp., with minimum inhibitory concentration (MIC)
of 1 µg/mL and MIC
of 2 µg/mL, respectively. Overall, AMB was less active than azoles against
spp. (MIC
: 4 µg/mL, MIC
: 8 µg/mL). Against the
order, ISA demonstrated MIC
of 0.5 µg/mL and MIC
of 1 µg/mL; however, one strain each of
and
were resistant to ISA (MICs: >8 µg/mL). VOR exhibited little or no activity (MIC
: 8 µg/mL, MIC
: >8 µg/mL) against the
order, whereas AMB had MIC
and MIC
of 1 µg/mL.
This was the first multicenter, in vitro study conducted in China and demonstrated the excellent activities of ISA against most species of the
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.
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