A plain language summary of how some fungi samples that show resistance to antifungal medicines have changes in their genes.

WHAT IS THIS SUMMARY ABOUT?: Aspergillus fumigatus (shortened to A. fumigatus) is a fungus (plural: fungi) that can cause a serious infection in some people. A. fumigatus can become resistant to medicines known as azoles (isavuconazole, itraconazole, posaconazole, and voriconazole). This means they stop working and are not able to kill the fungus. Fungi can become resistant through changes in their genes, which are called mutations. Scientists looked at previously collected samples from people infected with A. fumigatus and found that 36 of the samples showed resistance to an azole. In 35 of these samples, scientists looked for mutations in 50 genes. These 50 genes are known to play a role in azole resistance and/or are important for fungal survival. WHAT WERE THE RESULTS?: In total, 18 out of 36 samples (50%) showed resistance to isavuconazole only. Of these, 12 had mutations in 4 genes important for fungal survival (called erg3C, erg2, erg7B and erg4B). Mutations were found in 2 genes that are the most common causes of azole resistance (called cyp51A and cyp51B). The most common mutation, called cyp51A TR34/L98H, was found in 9 samples. Of these, 8 samples showed resistance to all 4 of the azoles tested. WHAT DO THE RESULTS OF THE STUDY MEAN?: Studying mutations that make fungi resistant to medicines helps to make sure that people with fungal infections get treated with medicines that will work for them.

In Vitro Selection of Enterobacter cloacae with Cefepime, Meropenem, and Ceftazidime-Avibactam Generates Diverse Resistance Mechanisms.

Five Enterobacter cloacae isolates were subjected to 10-day serial passage in broth microdilution with cefepime, meropenem, or ceftazidime-avibactam to evaluate increases in minimum inhibitory concentration (MIC) and resistance mechanisms after exposure. Post-exposure isolates displaying >2-fold changes from the parent isolate were analysed alongside the parent isolate. Increases in MIC were 4- to 256-fold (median: 16-fold) after cefepime exposure, 16- to 128-fold (64-fold) after meropenem, and 2- to 32-fold (8-fold) after ceftazidime-avibactam. Post-exposure isolates had diverse mechanisms, identified using a combination of short and long whole-genome sequencing. All agents selected for AmpC alterations in one isolate set. OmpC and TetA/AcrR regulator alterations were noted in meropenem and ceftazidime-avibactam post-exposure isolates of the same set. Other mutations in AmpC were noted when isolates were exposed to cefepime or ceftazidime-avibactam. A premature stop codon in the cell division inhibitor protein, MioC was observed when one parent isolate was exposed to any of the agents, indicating a cell persistence mechanism. Mutations in less common transporter systems and protein synthesis components were also noted. All agents showed cross-resistance to other ß-lactams and resistance mechanisms were diverse, with some not usually associated with ß-lactam resistance in Enterobacterales. This initial evaluation indicates that cefepime and meropenem select for isolates with higher MIC values compared to ceftazidime-avibactam. Further studies evaluating these findings should be performed for other species for which the primary ß-lactam resistance mechanism is not gene acquisition. These studies should evaluate these observations in vivo to assess their translation into patient treatment policies.

Political ideology and pandemic lifestyles: the indirect effects of empathy, authoritarianism, and threat.

Background: In this paper, we integrate theory and research from sociology, psychology, and political science to develop and test a mediation model that helps to explain why political conservatism is often associated with pandemic behaviors and lifestyles that are inconsistent with public health recommendations for COVID-19. Methods: Using national data from the 2021 Crime, Health, and Politics Survey (n = 1743), we formally test the indirect effects of political conservatism (an index of Republican party identification, conservative political orientation, right-wing news media consumption, and 2020 Trump vote) on pandemic lifestyles (an index of social distancing, hand sanitizing, mask usage, and vaccination) through the mechanisms of empathy (concern about the welfare of others), authoritarian beliefs (authoritarian aggressiveness and acquiescence to authority), and pandemic threat perceptions (threats to self and to the broader society). Result: Our results confirm that political conservatism is associated with riskier pandemic lifestyles. We also find that this association is partially mediated by lower levels of empathy, higher levels of authoritarian beliefs, and lower levels of perceived pandemic threat. Conclusions: Understanding why political conservatism is associated with riskier pandemic lifestyles may eventually lead us to ways of identifying and overcoming widespread cultural barriers to critical pandemic responses.

Azole resistance in Candida glabrata clinical isolates from global surveillance is associated with efflux overexpression.

OBJECTIVES: We evaluated the azole resistance mechanisms and epidemiology of fluconazole-resistant Candida glabrata from a global survey. METHODS: A total of 2992 Candida spp. isolates collected during 2018-2019 were susceptibility tested by the broth microdilution reference method following CLSI guidelines. Fluconazole-resistant C. glabrata isolates were submitted to whole genome sequencing and gene expression assays using qRT-PCR. RESULTS: Among 561 CGLA isolates tested, 34 (6.1%) were fluconazole resistant. These isolates were collected from 11 countries and mainly recovered from bloodstream infections (79.4%). All fluconazole-resistant C. glabrata isolates were non-wild type for voriconazole, 24/34 were non-wild type for posaconazole, but only 2/34 were non-wild type for itraconazole. Isavuconazole MIC values ranged from 0.25 to >4 mg/L. Fluconazole-resistant C. glabrata isolates belonged to 14 different sequence types (ST). None of the isolates exhibited alterations in ERG3 or ERG11, the target of azoles. All but two fluconazole-resistant isolates displayed overexpression of CgCDR1 (22/34; 64.7%) and/or CgCDR2 (26/34; 76.5%), while 16 isolates had both genes overexpressed. Overexpression of CgSNQ2 or ERG11 was not observed. Gain of function (GoF) alterations in the transcription factor CgPDR1 were noted in 14 isolates. Four (11.8%) isolates that were nonsusceptible to one or more echinocandins had FKS2 HS1 alterations (2 S663P and 2 F659Y/deletion). CONCLUSION: Fluconazole-resistant C. glabrata was driven by overexpression of CgCDR1 and/or CgCDR2. GoF alterations in PDR1 that have been associated with increased virulence were observed. Susceptibility results and surveillance data are needed to guide treatment for these isolates.

Characterization of Enterobacter cloacae and Citrobacter freundii species complex isolates with decreased susceptibility to cephalosporins from United States hospitals and activity of ceftazidime/avibactam and comparator agents.

OBJECTIVES: To evaluate the antimicrobial susceptibility and resistance mechanisms to ß-lactams among Enterobacter cloacae and Citrobacter freundii from United States medical centres. METHODS: 2571 E. cloacae and 1008 C. freundii species complex isolates were consecutively collected from 77 medical centres and susceptibility tested by broth microdilution method. Isolates displaying MIC values ≥16 mg/L for ceftazidime or ≥2 mg/L for cefepime (n = 914) were tested for ß-lactamase-encoding genes using whole genome sequencing. RESULTS: Overall susceptibility to ceftazidime and cefepime were 73.9% and 91.2% among E. cloacae and 74.2% and 93.5% among C. freundii, respectively. Sixty-three isolates harboured a carbapenemase gene, including 56 bla KPC, 2 bla NMC-A, and 5 metallo-ß-lactamase genes. Among non-carbapenemase producers, 121 isolates had at least one ESBL-encoding gene, mainly bla SHV (81) or bla CTX-M (61), and 15 had a transferable AmpC gene, mainly bla DHA-1 (8) or bla FOX-5 (6). Carbapenemase, ESBL, or transferable AmpC-encoding genes were not identified among 718 of 914 (78.6%) isolates sequenced. The most active agents against isolates with a decreased susceptibility to ceftazidime and/or cefepime were ceftazidime/avibactam (MIC50/90, 0.5/1 mg/L; 99.3% susceptible), amikacin (MIC50/90, 1/4 mg/L; 99.5% susceptible), and meropenem (MIC50/90, 0.06/0.5 mg/L; 92.9% susceptible). The isolates resistant to ceftazidime/avibactam were the five MBL producers and one E. cloacae isolate with a reduced expression of OmpF and overexpression of AcrAB-TolC. CONCLUSIONS: Hyperproduction of chromosomal AmpC appears to be the most common mechanism of resistance to ceftazidime and/or cefepime in E. cloacae and C. freundii. Ceftazidime/avibactam remained highly active against most isolates showing decreased susceptibility to ceftazidime and/or cefepime.

Charismatic authority and fractured polities: A cross-national analysis.

Sociological research has overlooked the political consequences of charismatic leadership that arises in existing democratic political bureaucracies. In this article, we theorize the consequences of charismatic leadership in democratic nations by revisiting Max Weber's theory of charismatic authority. Our extension of Weber's theory of charismatic authority helps to address a gap in the political polarization literature concerning the role of charismatic leadership. This article provides a foundational link in the research on charismatic authority-bridging the literatures on charisma and cross-national comparative sociology. This bridging is enabled by advances in data collection that include information on charismatic authority in cross-national context. This article makes use of a Driscoll and Kraay fixed-effects analysis across 76 democracies from 1960 to 2009 to explore the relationship between charismatic leadership and political polarization. Our findings suggest that nations with higher levels of charismatic leadership tend to have higher levels of political polarization. These results contribute to both the literature on political polarization and charisma-as well as support our extension of Weber's theory of charismatic authority.

Isavuconazole nonwildtype Aspergillus fumigatus isolates from a global surveillance study display alterations in multiple genes involved in the ergosterol biosynthesis pathway not previously associated with resistance to other azoles.

OBJECTIVES: We evaluated 35 azole nonwildtype Aspergillus fumigatus isolates that were collected during 2017-2018 using whole genome sequencing (WGS) to detect alterations in the genes involved in the ergosterol biosynthesis pathway as well as other genes associated with azole resistance. METHODS: Among 297 A fumigatus isolates collected worldwide, 36 isolates displayed nonwildtype MIC values to isavuconazole, itraconazole, or voriconazole when tested by the CLSI reference broth microdilution method. Isolates were submitted to WGS and results were compared to 2 azolewildtype isolates. RESULTS: Among the 35 sequenced isolates (1 failed to produce quality sequences), 29 were nonwildtype to isavuconazole, 16 were nonwildtype to itraconazole, and 9 were nonwildtype to voriconazole (CLSI M59Ed2 criteria). A total of 9 isolates carried Cyp51A TR34/L98H alterations (8 from Italy and 1 from Belgium) and had nonwildtype MIC values for ≥2 azoles. A Cyp51B Q42L mutation was detected in 3 isolates, 1 nonwildtype voriconazole and 2 nonwildtype isavuconazole isolates. Three isolates harboured multiple mutations in Cyp51A (F46Y, M172V, E427K ± N248T, and D255E), including 1 isolate with the Cyp51B Q42L mutation. Mutations causing frameshifts, early termination, and duplications were observed among several genes and were more prevalent in isavuconazole nonwildtype isolates (66.7%) than in the isolates that were nonwildtype to 1 or 2 other azoles (22.2%). Nine isolates harboured frameshift mutations in a ERG25 homologue that is usually associated with changes in other genes and should be further evaluated. CONCLUSIONS: Cyp51A L98H/TR34 was the most common alteration observed among the azole nonwildtype A fumigatus isolates from a large surveillance study; however, only isolates that were nonwildtype to isavuconazole had alterations in multiple analysed genes. These isolates deserve further evaluation.

Social scientists' testimony before Congress in the United States between 1946-2016, trends from a new dataset.

Congressional hearings are a venue in which social scientists present their views and analyses before lawmakers in the United States, however quantitative data on their representation has been lacking. We present new, publicly available, data on the rates at which anthropologists, economists, political scientists, psychologists, and sociologists appeared before United States congressional hearings from 1946 through 2016. We show that social scientists were present at some 10,347 hearings and testified 15,506 times. Economists testify before the US Congress far more often than other social scientists, and constitute a larger proportion of the social scientists testifying in industry and government positions. We find that social scientists' testimony is increasingly on behalf of think tanks; political scientists, in particular, have gained much more representation through think tanks. Sociology, and psychology's representation before Congress has declined considerably beginning in the 1980s. Anthropologists were the least represented. These findings show that academics are representing a more diverse set of organizations, but economists continue to be far more represented than other disciplines before the US Congress.

Happiness is a warm gun? Gun ownership and happiness in the United States (1973-2018).

Although there is no empirical evidence linking gun ownership with happiness, speculation is widespread. In this paper, we assess the association between gun ownership and happiness. We use 27 years of national cross-sectional data from the General Social Survey (1973-2018) and logistic regression to model self-rated happiness as a function of gun ownership (n = 37,960). In bivariate and partially adjusted models, we observed that the odds of being very happy were higher for respondents who reported having a gun in their home. This association persisted with adjustments for age, gender, race/ethnicity, education, employment status, household income, financial satisfaction, financial change, number of children, religious attendance, political affiliation, urban residence, region of interview, and survey year. In our fully adjusted model, gun ownership was unrelated to happiness. The original association between gun ownership and happiness was entirely confounded by marital status. In other words, gun owners only appeared happier because they are more likely to be married, which increases happiness. In the first study of gun ownership and happiness, we found that people who own guns and people who do not own guns tend to exhibit similar levels of happiness. This general pattern was consistent across nearly three decades of national surveys, a wide range of subgroups, and different measures of happiness. Our analyses are important because they contribute to our understanding of the epidemiology of happiness. They also indirectly challenge theoretical perspectives and cultural narratives about how guns contribute to feelings of safety, power, and pleasure.

In vitro activity of Plazomicin against Enterobacteriaceae isolates carrying genes encoding aminoglycoside-modifying enzymes most common in US Census divisions.

Aminoglycoside-nonsusceptible isolates of Escherichia coli, Klebsiella, Proteus, and Enterobacter species (480/3675) from US hospitals collected during 2014-2015 were screened for 16S rRNA methyltransferase and aminoglycoside-modifying enzyme (AME) genes. Only 5 isolates had high aminoglycoside MICs and carried 16S rRNA methyltransferases. AME genes were observed among 89.7% (426/475) of isolates and the most common genes were aac(3)-IIa (n = 270) and aac(6')-Ib (n = 269). Among other genes, ant(2″)-Ia, aac(3)-Iva, and aph(3')-VIa were observed among 36, 23, and 3 isolates, respectively. Forty-nine (10.3%) isolates yielded negative results for the investigated AME genes. Plazomicin (MIC50/90, 0.5/1 µg/ml) inhibited 99.3% of the AME-carrying isolates at its susceptible breakpoint while amikacin, gentamicin, and tobramycin inhibited 90.1%, 20.9%, and 18.3%, respectively. Plazomicin was approved by the US Food and Drug Administration in June 2018 for the treatment of complicated urinary tract infections when limited treatment options are available. This agent displayed activity against isolates carrying AMEs that were resistance to other aminoglycosides and comparator agents.

Aminoglycoside-modifying enzyme and 16S ribosomal RNA methyltransferase genes among a global collection of Gram-negative isolates.

OBJECTIVES: The prevalence of genes encoding aminoglycoside-modifying enzymes (AMEs) and 16S rRNA methyltransferases among 200 Gram-negative clinical isolates resistant to different aminoglycosides and collected worldwide during 2013 was evaluated. METHODS: Selected AMEs and 16S rRNA methyltransferase genes were screened by PCR/sequencing among 49 Acinetobacter spp., 52 Pseudomonas aeruginosa and 99 Enterobacterales. RESULTS: In total 72 isolates carried aac(6')-lb variants (36.0% overall; 55.6% Enterobacterales): 30 aac(6')-Ib-cr, 21 aac(6')-Ib and 21 aac(6')-Ib-like displaying substitutions L119S (alone or in combination with V71A or R173K) or S100G. Ten aph(3')-VI variants were detected among 35 isolates (46.9% of Acinetobacter spp.). Nineteen isolates carried variants of aac(3)-I, with aac(3)-Ia (n=13, mostly Acinetobacter spp.) being the most prevalent. Other AME genes detected were ant(3″)-Ia (n=41), ant(2″)-Ia (n=24), aac(3)-IIe (n=23), aac(3)-IId (n=21), aac(6')-Im (n=13, mostly P. aeruginosa), aacA8 (n=3), aac(3)-IIf (n=1) and aac(3)-IVa (n=1). Among 42 isolates resistant to amikacin, gentamicin and tobramycin tested for 16S rRNA methyltransferase genes, 21 (50.0%) tested positive; armA was most common (n=14), but 4 isolates carried rmtB1, 2 rmtF1 and 1 new variant rmtB4. Over 60 gene combinations, consisting of one to four AMEs and 16S rRNA methyltransferases, were observed. Cloning genes not previously characterised revealed diverse aminoglycoside resistance patterns for some AMEs, but expected results for rmtB4. CONCLUSIONS: Studies broadly evaluating these aminoglycoside resistance genes are needed. Using agents stable in the presence of these resistance genes might help overcome resistance.

Analyses of a Ceftazidime-Avibactam-Resistant Citrobacter freundii Isolate Carrying blaKPC-2 Reveals a Heterogenous Population and Reversible Genotype.

A blaKPC-2-carrying Citrobacter freundii isolate developed ceftazidime-avibactam resistance during treatment with this agent. The initial and follow-up isolates exhibited ceftazidime-avibactam MICs of 4 and 64 µg/ml, respectively. Overexpression of AcrAB-TolC and porin alterations were detected in both isolates, but no other resistance mechanism was observed. After passaging the initial clinical isolate in ceftazidime-avibactam at a fixed concentration of 4 µg/ml and a 4:1 ratio, resistance to all ß-lactams was noted, and a percentage of the blaKPC-2 sequencing reads had mutations leading to the alterations D176Y (blaKPC-2-D176Y [78%]) or R164S plus P147L (blaKPC-2-R164S + P147L [82%]). Further investigation of the follow-up isolate showed that 11% of the blaKPC-2 reads had mutations leading to D179Y substitution (blaKPC-2-D179Y). In the absence of selective pressure, ceftazidime-avibactam MICs of the passaged and follow-up isolates revealed that 7 or 8 out of 20 screened colonies reverted to susceptible and possessed blaKPC-2 wild-type sequences. Recombinant plasmids carrying the blaKPC-2 alterations observed were transformed in Escherichia coli, and MIC values for ceftazidime ± avibactam were elevated. Lower MICs for ceftriaxone, cefepime, aztreonam, meropenem, and imipenem for the mutated KPC-2-producing isolates were observed compared to those of the isolates producing a wild-type KPC-2. Avibactam at a fixed concentration of 4 µg/ml restored the activity of all ß-lactams tested for the recombinant strains. The heterogenous population of wild-type and mutated blaKPC-2 and the reversibility of the genotypes observed suggest a significant challenge for managing KPC-producing isolates that develop ceftazidime-avibactam resistance during therapy.IMPORTANCE The development of ceftazidime-avibactam resistance among KPC-producing isolates during treatment with this agent has been reported. Usually isolates that become resistant have a mutated blaKPC gene that confers resistance to ceftazidime-avibactam and susceptibility to meropenem. We report a Citrobacter freundii isolate that developed ceftazidime-avibactam resistance due to mutations within the coding region of the blaKPC-2 Ω-loop previously reported; however, in this case, only 11% of the whole-genome sequencing reads had mutations, making this alteration difficult to detect and the treatment of these isolates more challenging. In addition to blaKPC, the initial and the follow-up patient isolates displayed hyperexpression of the AcrAB-TolC efflux system and disruption of the outer membrane protein (OMP) OmpF, which contribute to carbapenem resistance. Experiments performed to confirm our findings included generating mutant isolates from the initial patient isolate, passaging the isolates for purity in drug-free medium, resulting in a reversible phenotype, and cloning the mutations to demonstrate the resistance conferred.

In Vitro Activity of Plazomicin against Gram-Negative and Gram-Positive Isolates Collected from U.S. Hospitals and Comparative Activities of Aminoglycosides against Carbapenem-Resistant Enterobacteriaceae and Isolates Carrying Carbapenemase Genes.

Plazomicin and comparator agents were tested by using the CLSI reference broth microdilution method against 4,825 clinical isolates collected during 2014 and 2015 in 70 U.S. hospitals as part of the ALERT (Antimicrobial Longitudinal Evaluation and Resistance Trends) program. Plazomicin (MIC50/MIC90, 0.5/2 µg/ml) inhibited 99.2% of 4,362 Enterobacteriaceae at ≤4 µg/ml. Amikacin, gentamicin, and tobramycin inhibited 98.9%, 90.3%, and 90.3% of these isolates, respectively, by applying CLSI breakpoints. The activities of plazomicin were similar among Enterobacteriaceae species, with MIC50 values ranging from 0.25 to 1 µg/ml, with the exception of Proteus mirabilis and indole-positive Proteeae that displayed MIC50 values of 2 µg/ml. For 97 carbapenem-resistant Enterobacteriaceae (CRE), which included 87 isolates carrying blaKPC, plazomicin inhibited all but 1 isolate at ≤2 µg/ml (99.0% and 98.9%, respectively). Amikacin and gentamicin inhibited 64.9% and 56.7% of the CRE isolates at the respective CLSI breakpoints. Plazomicin inhibited 96.5 and 95.5% of the gentamicin-resistant isolates, 96.9 and 96.5% of the tobramycin-resistant isolates, and 64.3 and 90.0% of the amikacin-resistant isolates according to CLSI and EUCAST breakpoints, respectively. The activities of plazomicin against Pseudomonas aeruginosa (MIC50/MIC90, 4/16 µg/ml) and Acinetobacter species (MIC50/MIC90, 2/16 µg/ml) isolates were similar. Plazomicin was active against coagulase-negative staphylococci (MIC50/MIC90, 0.12/0.5 µg/ml) and Staphylococcus aureus (MIC50/MIC90, 0.5/0.5 µg/ml) but had limited activity against Enterococcus spp. (MIC50/MIC90, 16/64 µg/ml) and Streptococcus pneumoniae (MIC50/MIC90, 32/64 µg/ml). Plazomicin activity against the Enterobacteriaceae tested, including CRE and isolates carrying blaKPC from U.S. hospitals, supports the development plan for plazomicin to treat serious infections caused by resistant Enterobacteriaceae in patients with limited treatment options.

Case report of transient mcr-1-haboring Escherichia coli with concurrent Staphylococcus aureus bacteremia in Long Beach, California.

A 55-year-old man with history of chronic hepatitis B cirrhosis presented to an emergency department in California with abdominal pain, constipation, and jaundice. The patient developed methicillin-susceptible S. aureus bacteremia with a concurrent transient E. coli. This organism carried mcr-1 in a plasmid similar to other mcr-1-carrying plasmids from the USA. The spread of mcr-1 into carbapenem-resistant isolates is of great concern and monitoring of this resistance mechanism is important.

A social ecology of civil conflict: Shifting allegiances in the conflict in Sierra Leone.

Drawing on data from a survey of 1043 ex-combatants who took part in the civil war in Sierra Leone (1991-2002) this paper explores the conditions that predict a key outcome in the conflict literature: defection, or side-switching between the various organizations at war. This paper advances arguments drawn from the organizational ecology school and works to extend key theories related to "Blau Space" to the study of civil war. Using a series of logistic regression procedures, this paper tests various competing hypotheses against key contributions of the organizational ecology school. Key findings of this work suggest support for major hypotheses in this literature as net of important theoretical conditions, defections are most likely when individuals are either demographically atypical of their organization (niche edge) or most susceptible to competition for their services by other groups (niche overlap).

Monitoring Antifungal Resistance in a Global Collection of Invasive Yeasts and Molds: Application of CLSI Epidemiological Cutoff Values and Whole-Genome Sequencing Analysis for Detection of Azole Resistance in Candida albicans.

The activity of 7 antifungal agents against 3,557 invasive yeasts and molds collected in 29 countries worldwide in 2014 and 2015 was evaluated. Epidemiological cutoff values (ECVs) published in the Clinical and Laboratory Standards Institute (CLSI) M59 document were applied for species with no clinical breakpoints. Echinocandin susceptibility rates were 95.9% to 100.0% for the 5 most common Candida species, except for the rates for Candida parapsilosis to anidulafungin (88.7% susceptible, 100.0% wild type). Rates of fluconazole resistance ranged from 8.0% for Candida glabrata to 0.4% for Candida albicans Seven Candida species displayed 100.0% wild-type amphotericin B MIC results, and Candida dubliniensis and Candida lusitaniae exhibited wild-type echinocandin MIC results. The highest fluconazole, voriconazole, and posaconazole MIC values for Cryptococcus neoformans var. grubii were 8 µg/ml, 0.12 µg/ml, and 0.25 µg/ml, respectively. Aspergillus fumigatus isolates were 100.0% wild type for caspofungin and amphotericin B, but 3 (0.8%) of these isolates were non-wild type to itraconazole (2 isolates) or voriconazole (1 isolate). Mutations in FKS hot spot (HS) regions were detected among 13/20 Candida isolates displaying echinocandin MICs greater than the ECV (16 of these 20 isolates were C. glabrata). Most isolates carrying mutations in FKS HS regions were resistant to 2 or more echinocandins. Five fluconazole-nonsusceptible C. albicans isolates were submitted to whole-genome sequencing analysis. Gain-of-function, Erg11 heterozygous, and Erg3 homozygous mutations were observed in 1 isolate each. One isolate displayed MDR1 promoter allele alterations associated with azole resistance. Elevated levels of expression of MDR1 or CDR2 were observed in 3 isolates and 1 isolate, respectively. Echinocandin and azole resistance is still uncommon among contemporary fungal isolates; however, mechanisms of resistance to antifungals were observed among Candida spp., showing that resistance can emerge and monitoring is warranted.

A fully adjustable suture for trabeculectomy.

Most approaches to improve the control of intraocular pressure (IOP) in the early postoperative period following trabeculectomy involve irreversible alterations of the flap sutures, which carry subsequent risk of overfiltration. A new technique using a fully adjustable suture that can be incrementally loosened or tightened is described. Eighteen eyes underwent trabeculectomy using a fully adjustable suture. Suture adjustments were made in the early postoperative period based on IOP, bleb appearance, and the results of digital massage. Sixteen of the 18 eyes were able to maintain the target IOP level without additional drops or laser treatment. The use of a fully adjustable suturing technique is safe and allows excellent control of IOP in the early postoperative period.