Carbon dioxide is an effective anesthetic for multiple marine fish species

Most marine fish culture is still experimental, but in the last decade or so, many new marine and diadromous food fish species have reached the pilot or commercial stage. Established and new species include: sturgeons, anguillid eels, milkfish, salmonids, barramundi, European sea bass, hybrid striped bass, a few groupers, yellowtail, dolphin, red sea bream, black sea bream, gilthead sea bream, red drum, tilapias, mullets, rabbitfishes, turbot, Atlantic halibut, and tiger puffer.

Old Drugs, New Concerns

BackgroundAztreonam-avibactam (ATM-AVI) was recently approved by the United States (US) Food and Drug Administration (FDA) for the treatment of intra-abdominal infections. ATM-AVI has shown potent activity against multidrug-resistant (MDR) Enterobacterales, including metallo-β-lactamase (MBL) producers. We evaluated the antimicrobial susceptibility of Enterobacterales and P. aeruginosa (PSA) of immunosuppressed patients from US medical centers.Antimicrobial susceptibility of Enterobacterales and resistant subsets of isolates from immunosuppressed patientsa Carbapenemase-producing CRE isolates.Abbreviations: CLSI, Clinical and Laboratory Standards Institute; US FDA, United States Food and Drug Administration; MDR, multidrug-resistant; CRE, carbapenem-resistant Enterobacterales; CBase, carbapenemase.Antimicrobial susceptibility of selected species collected from immunosuppressed patientsa % inhibited at ≤8 mg/L, the CLSI breakpoint for aztreonam. b Not tested or no breakpoint published by US FDA.Abbreviations: CLSI, Clinical and Laboratory Standards Institute; US FDA, United States Food and Drug AdministrationMethodsBacterial isolates were consecutively collected (1/patient) from 75 US medical centers in 2019-2024 and susceptibility tested by broth microdilution. Enterobacterales and PSA from patients hospitalized in hematology, oncology, and transplant units were evaluated. Carbapenem-resistant Enterobacterales (CRE; isolates with MIC ≥ 4 mg/L for meropenem and/or imipenem) were screened for β-lactamase by whole genome sequencing.ResultsEnterobacterales were mainly from bloodstream infection (BSI; 53.6%) and urinary tract infection (UTI; 19.9%) and PSA were mainly from BSI (37.9%) and pneumonia (35.0%). ATM-AVI, ceftazidime-avibactam (CAZ-AVI), and meropenem-vaborbactam (MEM-VAB) were highly active against Enterobacterales (99.9-99.4% susceptible [S]), including MDR isolates (99.6-98.1% S; Table 1), ATM-AVI retained potent activity against CRE isolates (95.8% S). Ceftolozane-tazobactam (TOL-TAZ) showed good activity against E. coli (95.7% S), and K. pneumoniae (92.8% S), but limited activity against E. cloacae species complex (75.9% S; Table 2). All (100.0%) carbapenemase (CBase)-producing CRE isolates were ATM-AVI-S while 77.4% were CAZ-AVI-S and 67.7% were MEM-VAB-S. The most common CBases were KPC (61.3%), NDM (16.1%), and OXA-48 types (16.1%). MBL represented 19.4% of CBases. The most active agents against PSA were CAZ-AVI (95.7% S), TOL-TAZ (94.8% S), and tobramycin (91.5% S). PIP-TAZ and meropenem were active against 81.4% and 82.5% of PSA, respectively, and ATM-AVI inhibited 78.6% of PSA at ≤8 mg/L.ConclusionATM-AVI demonstrated almost complete activity (99.9% S) against Enterobacterales, including 100.0% of CBase producers, and both CAZ-AVI and TOL-TAZ were highly active against PSA from immunosuppressed patients.DisclosuresHelio Sader, United States Food and Drug Administration: FDA Contract Number: 75F40123C00140 Mariana Castanheira, PhD, Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support Rodrigo E. Mendes, PhD, GSK: Grant/Research Support|Shionogi & Co., Ltd.: Grant/Research Support|United States Food and Drug Administration: FDA Contract Number: 75F40123C00140

Fish is an important source of protein in human meals around the world. However, the fish that we are eating may be contaminated with toxicants such as metals and metalloids (MMs), which may pose health risks to consumers. Information on MMs content in fishes and their potential spatial distribution scenarios would provide knowledge to the community to create strategies and protect human health. Hence, this study assessed and determined the health risk levels of MMs in both brackish and marine water fish (BMF) in Puerto Princesa City (PPC), Palawan Province, Philippines. PPC has an existing abandoned open mine pit near the PPC coastline called the “pit lake”. The concentrations of As, Ba, Cu, Fe, Mn, Hg, and Zn in fishes were analyzed using portable Olympus Vanta X-ray Fluorescence (pXRF), and the spatial distribution of MMs concentrations in BMF was analyzed using a GIS (geographic information system). Fishes were sampled from fishing boat landing sites and nearby seafood markets. The results revealed that the concentration of MMs in marine fish was generally higher than the brackish water fish. It was recorded that the Hg concentration in marine water fish meat was higher than in brackish water fish meat. The Mn concentration in marine water fish exceeded the permissible limits set by international bodies. An elevated concentration of Mn in BMF was detected across the northern part of PPC, and an elevated concentration of Hg in marine fishes was recorded in the southeast area, where the fish landing sites are located. Ba was also detected in BMF across the southern part of PPC. Moreover, an elevated concentration of Cu was detected in MBF in the northeast and in marine fish in the southeastern area of PPC. Further, this paper elaborates the non-carcinogenic and carcinogenic risks of these fishes to the PPC population and tourists with respect to the MMs content in fish meat.

Sequestration of total and methyl mercury in different subcellular pools in marine caged fish

A series of growth trials was conducted to evaluate the use of soy protein as a replacement for fish protein in isonitrogenous practical diets for juvenile red drum Sciacnops ocellatus. Feeds were offered at or in excess of satiation to juvenile red drum maintained at 26–28 C and a salinity of 25–35 ppt. In the first growth trial, red drum were offered one of four diets containing graded levels of menhaden fish meal, replacing solvent‐extracted soybean meal and soy‐protein isolates. Differences in weight gain, survival and feed efficiency ratios of the fish corresponded to increases in fish meal content of the diets. Due to poor performance of the fish maintained on the low (15%) fish meal diet, a methionine supplement was introduced into this diet at the midpoint of the growth trial. A positive increase in growth indicated a dietary deficiency of methionine and/or total sulfur amino acids in the unsupplemented diet. A positive response to dietary fish meal also occurred in the second growth trial despite the supplementation of L‐methionine in the test diets. In low fish meal diets the utilization of solvent extracted soybean meal or a soy‐protein isolate resulted in similar growth responses. Hence, the presence of an antinutrient did not likely cause reduced growth rates. In the third feeding trial, weight gain also increased with increasing fish meal content of the diet despite the equalization of digestible protein and selected amino acids. There were no significant differences in whole‐body compositions which indicated similar biological value of the diets (protein digestibility, amino acid balance and energy availability). The singular deletion of fish‐solubles, glycine, lysine and methionine from the diet containing the lowest level of fish meal (10 g/100 g diet) did not result in significant changes in weight gain. This indicated that these components did not add to the nutritive value and/or palatability of this formulation. The final experiment was designed to evaluate the response of red drum to a control diet (high fish meal) as compared to a low fish meal diet with and without potential attractants/palatability enhancers. Weight gain and feed efficiency ratios of fish offered the low fish meal diet supplemented with seafood flavor or fish flavor #2 were not significantly different from the control (high fish meal diet). Based on the results of this study, with suitable formulation restrictions, soy protein is acceptable for inclusion in practical diet formulations for red drum. However, soy protein itself does not appear replete in sulfur‐containing amino acids and does not have acceptable palatability properties. Consequently, feeds containing reduced levels of marine proteins could require suitable attractants and/or amino acid supplements.

Black soldier fly (Hermetia illucens) larvae are insects capable of valorizing various waste streams into protein that has the potential to replace fish meal (FM) in fish diets. To evaluate the feasibility of replacing FM with black soldier fly meal (BSFM) in the diet of red drum (Sciaenops ocellatus) juveniles, a two-part study was conducted that included a palatability trial followed by an 8-week feeding trial with isonitrogenous and isoenergetic formulations. Red drum is a marine and brackish-water fish species found in the Western Atlantic, ranging from Massachusetts, southern Florida, and the Gulf to northern Mexico. The palatability trial was conducted with BSFM replacing FM in diets at 0% (Control), 25% (BSFM25), 50% (BSFM50), and 100% (BSFM100) levels. The palatability assessment showed that the red drum feeding response was statistically similar between the Control and BSFM25 diets. The feeding trial included the diets above plus BSFM replacing FM at 75% (BSFM75), and the effects on growth, feeding efficiency, whole-body biochemical composition, intestinal/liver histomorphology, and intestinal microbiome were assessed. Better growth and feeding efficiency (P<0.05) were observed in fish fed the BSFM25 diet compared to those fed the BSFM50, BSFM75, and BSFM100 diets. Whole-body saturated fatty acids increased with higher levels of BSFM in the diet, while the levels of arachidonic acid (ARA), eicosapentanoic acid (EPA), and docosahexaenoic acid (DHA) remained statistically similar in BSFM25 and BSFM50 compared to the Control. Liver histomorphology revealed increased hepatic vacuolization with increasing levels of BSFM. Intestinal microbiota presented high alpha diversity abundance among the treatments, but the fish fed the BSFM diets tended to have genera associated with chitinase and lipase activity. Overall, dietary FM replacement with BSFM is an adequate alternative protein source with replacement up to 50%, but levels over 75% caused a reduction in growth and hepatic lipid accumulation.

BackgroundAztreonam-avibactam (ATM-AVI) was recently approved by the United States (US) Food and Drug Administration (FDA) for the treatment of intra-abdominal infections. Difficult-to-treat resistant (DTR) isolates, defined as bacterial isolates expressing nonsusceptibility to all first-line agents, is a major problem worldwide. We evaluated the activity of ATM-AVI and comparators against DTR Enterobacterales from US medical centers.Table 1.Antimicrobial susceptibility of selected resistant subsetsa Includes only DTR isolates. Abbreviations: DTR, difficult-to-treat resistant; CAZ-AVI, ceftazidime-avibactam; NS, nonsuscpetible; MEM-VAB, meropenem-vaborbactam; CRE, carbapenem-resistant Enterobacterales.Distribution of carbapenemase (CBase) types among difficult-to-treat (DTR) and carbapenem-resistant (CRE) isolatesMethods42,295 Enterobacterales isolates were consecutively collected (1/patient) from 85 US medical centers in 2020-2024 and susceptibility tested by CLSI broth microdilution. The collection included 450 carbapenem-resistant (CRE; defined as resistant [R] to meropenem or imipenem) and 307 DTR (defined as a fluoroquinolone-R CRE) isolates; which were screened for β-lactamases by whole genome sequencing.ResultsATM-AVI was active (MIC ≤ 4 mg/L) against 98.0% of DTR (MIC50/90, 0.25/1 mg/L) and 97.1% of CRE (MIC50/90, 0.25/1 mg/L) isolates, and retained potent activity against DTR isolates nonsusceptible (NS) to ceftazidime-avibactam (CAZ-AVI; 95.5% susceptible [S]; MIC50/90, 0.25/1 mg/L), meropenem-vaborbactam (MEM-VAB; 96.2% S; MIC50/90, 0.25/1 mg/L), and/or cefiderocol (90.0% S; MIC50/90, 0.5/4 mg/L; Table 1). Cefiderocol was active against 93.5% of DTR isolates, whereas CAZ-AV, MEM-VAB, IMI-REL and the aminoglycosides exhibited limited activity against these organisms. ATM-AVI (MIC50/90, 0.12/0.5 mg/L and cefiderocol (MIC50/90, 2/8 mg/L) were active against 97.7% and 86.4% of MBL producers, respectively. The most common carbapenemase (CBase) gene identified among DTR isolates were blaKPC (53.1% of isolates) and blaNDM (25.7%). DTR and CRE isolates exhibited similar frequencies of CBase types. An MBL gene was observed in 27.4% of DTR and 24.2% of CRE isolates (Figure 1).ConclusionATM-AVI retained potent activity against DTR Enterobacterales from US medical centers and its activity was not adversely affected by clinically relevant CBases or resistance to agents used to treat multidrug-resistant Enterobacterales. The activities of other β-lactamase inhibitor combinations and cefiderocol were compromised by the increased occurrence of MBL producers among DTR and CRE isolates.DisclosuresHelio Sader, United States Food and Drug Administration: FDA Contract Number: 75F40123C00140 Rodrigo E. Mendes, PhD, GSK: Grant/Research Support|Shionogi & Co., Ltd.: Grant/Research Support|United States Food and Drug Administration: FDA Contract Number: 75F40123C00140 Marisa Winkler, MD, PhD, Basilea: Advisor/Consultant|Basilea: Grant/Research Support|GSK: Advisor/Consultant|GSK: Grant/Research Support|Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pulmocide: Advisor/Consultant|Pulmocide: Grant/Research Support Mariana Castanheira, PhD, Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support

Background Aztreonam-avibactam (ATM-AVI) was approved by the United States (US) Food and Drug Administration (FDA) in February 2025. ATM-AVI has shown potent activity against multidrug-resistant (MDR) Enterobacterales, including metallo-β-lactamase (MBL) producers. We evaluated activity of ATM-AVI and comparators against isolates nonsusceptible (NS) to ceftazidime-avibactam (CAZ-AVI) and/or meropenem-vaborbactam (MEM-VAB) and against MBL producers.Table 1.Antimicrobial susceptibility of resistant subsetsAbbreviations: CAZ-AVI, ceftazidime-avibactam; NS, nonsusceptible; CRE, carbapenem-resistant Enterobacterales; MBL, metallo-β-lactamase; MEM-VAB, meropenem-vaborbactam; ATM-AVI, aztreonam-avibactam; IMI-REL, imipenem-relebactam.Finlandogram showing the activity of aztreonam-avibactam against selected resistant subsets. Methods 80,927 Enterobacterales isolates were consecutively collected (1/patient) in 2016–2024 from 103 US medical centers. Among these isolates, 194 (0.24%) were NS to CAZ-AVI or MEM-VAB, 115 (0.14%) were NS to both CAZ-AVI and MEM-VAB, and 832 isolates were carbapenem-resistant (CRE). Isolates were susceptibility tested by broth microdilution and screened for carbapenemase (CBase) genes by whole genome sequencing. Cefiderocol was tested in iron-depleted media. US FDA breakpoints were applied for ATM-AVI.Distribution of carbapenemase (CBase) typesAbbreviations: NS, nonsusceptible; CAZ-AVI, ceftazidime-avibactam; MEM-VAB, meropenem-vaborbactam; CRE, carbapenem-resistant Enterobacterales. Results ATM-AVI was active (MIC ≤4 mg/L) against 91.9% of CAZ-AVI-NS, 94.0% of MEM-VAB-NS, 98.1% of CRE and 98.3% of MBL-producing isolates (Table 1 and Figure 1). Cefiderocol retained activity against 78.8% of CAZ-AVI-NS, 83.2% of MEM-VAB-NS, 94.7% of CRE and 83.2% of MBL-producing isolates. Amikacin was the most active compound among non-β-lactams, it inhibited 63.1% of CAZ-AVI-NS and 61.1% of CRE isolates at CLSI susceptible breakpoint. A CBase was identified in 154 (79.4%) of isolates NS to CAZ-AVI or MEM-VAB and 673 (80.9%) of CREs. NDM (n=110; 56.7% of isolates) was the most common CBase type among isolates NS to CAZ-AVI or MEM-VAB, whereas KPC (n=525; 63.1% of CREs) and NDM (n=109; 13.1%) were the most common CBase types among CREs (Figure 2). Notably, a MBL was identified in 34.2% (69/202) of CREs collected in 2023-2024. Conclusion ATM-AVI demonstrated potent activity against isolates NS to CAZ-AVI and/or MEM-VAB as well as against CRE isolates, including MBL producers. The activities of other β-lactamase inhibitor combinations and cefiderocol were compromised by the increasing occurrence of MBL producers in US medical centers. Disclosures Helio Sader, United States Food and Drug Administration: FDA Contract Number: 75F40123C00140 Rodrigo E. Mendes, PhD, GSK: Grant/Research Support|Shionogi & Co., Ltd.: Grant/Research Support|United States Food and Drug Administration: FDA Contract Number: 75F40123C00140 Mariana Castanheira, PhD, Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support

Advances in development of long-term embryonic stem cell-like cultures from a marine fish, Sciaenops ocellatus

Background Gepotidacin (GEP) is a novel, bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct binding site, a unique mechanism of action and provides well-balanced inhibition of two type II topoisomerases (for most pathogens). GEP was recently approved by the United States (US) Food and Drug Administration (FDA) for the treatment of uncomplicated urinary tract infections (uUTI). This study reports the activity of GEP and other oral agents against E. coli (EC) and K. pneumoniae (KPN), including characterized fluoroquinolone (FQ) not susceptible (NS) isolates. Methods 1,409 isolates (1,011 EC and 398 KPN) from 58 US sites were included. CLSI methods were used for both susceptibility testing and MIC interpretation, except for GEP that used FDA breakpoints. Isolates that were NS to ciprofloxacin and/or levofloxacin were screened for FQ resistance (R) mechanisms (QRDR mutations, plasmid-mediated genes [PMQR]). Results GEP had MIC50/90 values of 2/4 µg/mL against all EC, and inhibited all (100%) isolates at the FDA S clinical breakpoint of ≤16 µg/mL. Among comparators, only nitrofurantoin was active against more than 90% of EC. A total of 19.7% of EC were FQ-NS. GEP had MIC90 values of 4 µg/mL against FQ-NS EC, regardless of FQ R mechanisms, and all FQ-NS EC were S to GEP. GEP (MIC50/90, 4/16 µg/mL) was active against 92.5% of all KPN, while amoxicillin-clavulanate (MIC50/90, 2/8 µg/mL) showed the highest S result (90.4%) among comparators. Among KPN isolates, 17.8% were FQ-NS, and GEP (MIC50/90, 16/64 µg/mL) inhibited 64.8% of these isolates at the S breakpoint. At the S breakpoint, GEP inhibited 89.5% to 100% of FQ-NS KPN isolates with QRDR mutations, regardless of the presence of PMQR. GEP had MIC50/90 values of 16/64 µg/mL against FQ-NS KPN with wildtype QRDR, including those that carried PMQR. Conclusion GEP demonstrated activity, with 100% susceptibility, against both FQ-S and FQ-NS EC causing UTIs in US medical centers, regardless of FQ R mechanisms. GEP was highly active against FQ-S KPN, and showed activity higher than comparator agents against FQ-NS KPN. These data benchmark GEP against EC and KPN for subsequent monitoring following its recent FDA approval for the treatment of uUTIs. Disclosures Rodrigo E. Mendes, PhD, GSK: Grant/Research Support|Shionogi & Co., Ltd.: Grant/Research Support|United States Food and Drug Administration: FDA Contract Number: 75F40123C00140 Renuka Kapoor, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Nicole E. Scangarella-Oman, MS, GSK: Employee|GSK: Stocks/Bonds (Public Company)

The relationship between predator gape and prey consumption in laboratory-reared larva and field-caught early juvenile red drum, Sciaenops ocellatus, was investigated in light of the hypothesis that feeding success varies throughout the early life history intervals of marine fishes. We expected the feeding ability of red drum to be more strongly constrained by mouth gape in smaller fish and expected this ability to improve with gape size. To test this hypothesis, field-caught, early juvenile red drum were examined to determine the relationship between gape size and prey size consumed. In field-caught early juveniles, gape (height and width) and prey size consumed (length and width) increased linearly with standard length (SL); however, mean width of prey consumed was only 20–47% of gape width. Furthermore, when regressed on SL, gape width yielded a higher slope than prey width. To further test this hypothesis on less developed, pre-metamorphic fish, age-specific differences in gape, number of prey and size of prey consumed prior to metamorphosis were determined from laboratory-reared red drum larvae. Similar patterns were observed for gape height– and gape width–SL relationships in laboratory-reared red drum larvae. Size of consumed prey increased from three days from hatching (dfh) to 18 dfh. The percentage of feeding larvae also increased from ∼3% at 3 dfh to 97% at 18 dfh. In both field-caught, early juvenile red drum and laboratory-reared larvae, there was little evidence that the size of prey consumed was constrained by mouth gape. It is hypothesized that besides gape size, the development of other features of the feeding mechanism (e.g., hyoid and opercular series) influences prey-capture performance prior to settlement in marine fishes.

Restriction-site variation in mitochondrial (mt) DNA was assayed among 1675 red drum (Sciaenops ocellatus Linnaeus) sampled from 20 localities along the southeastern coast of the USA (western Atlantic) and the Gulf of Mexico (Gulf). Up to four consecutive year-classes (cohorts) were sampled at most localities. Nucleotide-sequence divergence among 170 mtDNA haplotypes identified ranged (in percentage) from 0.184 to 1.913, with a mean (±SD) of 0.887 ± 0.300. Comparisons of mtDNA haplotype frequencies across year-classes within localities were non-significant, indicating temporal stability of breeding components within localities. Significant heterogeneity in mtDNA haplotype frequencies was found across all localities, between (pooled) samples from the western Atlantic and the Gulf, and among geographically spaced, regional groupings in the Gulf. Genetic divergence between subpopulations of red drum in the western Atlantic and Gulf follows a pattern exhibited in other marine fishes, and probably stems from physical (historical environmental heterogeneity, absence of suitable habitat, and current patterns) and, perhaps, behavioral factors. Genetic differences among red drum in the Gulf appear to be due largely to an isolation-by-distance effect that is attributable to behavioral factors. The latter may include female philopatry to natal bays or estuaries, limited offshore (coastwise) movement of females relative to their natal bay or estuary, or both. Genetic divergence among red drum in the Gulf occurs despite high gene flow (estimated as the number of genetic effective migrants in an island mode). Conservation and management of red drum should be based on the premise that strategies for a given bay or estuary will impact geographically proximal bays or estuaries more than distal ones. Trajectories of correlograms in spatial autocorrelation analysis suggest a geographic neighborhood size, relative to genetic migration of red drum from a bay or estuary, of roughly 500 to 600 km.

The identification of factors contributing to strong year classes of marine fishes has been a constant goal toward a mechanistic understanding of recruitment variability. Here, we explored a 26‐year time series of the abundance of early juvenile red drum along the North Carolina coast to identify environmental features associated with variable recruitment success. The study location was near the northern edge of the species latitudinal range, and we hypothesized that consistent environmental forcing would be linked to the formation of strong red drum year classes. Patterns of variability in seasonal environmental features were disaggregated into multiple forms of temporal periodicity and analyzed using generalized additive models. We also contrasted patterns of environmental variation that occurred during the strongest recruitment events with those coinciding with the weakest red drum year classes. The early shift, during August, to favorable wind conditions was the most consistent environmental feature associated with red drum recruitment success. The combined duration and magnitude of N and NE winds during August of strong recruitment years was nearly double the level observed during weak recruitment years. Elevated nearshore sea surface temperatures early in the spawning season were also found to occur during years that produced strong year classes. Coastal productivity, indexed using chlorophyll a concentration, was positively associated with red drum recruitment, but also highlighted the need for more spatially resolved productivity data. Our findings highlight the importance of environment‐recruitment linkages for marine fishes, especially near distributional boundaries where conditions to promote year class success can be brief.

Evaluation of growth performance, condition indices and body composition of juvenile red drum (Sciaenops ocellatus) fed fishmeal- and fish-oil-free diets