The intensification of production practices in the aquaculture industry has led to the indiscriminate use of antibiotics to combat diseases and reduce costs, which has resulted in environmental pollution, posing serious threats to aquaculture sustainability and food safety. However, the toxic effect of florfenicol (FF) exposure on the hepatopancreas of crustaceans remains unclear. Herein, by employing Chinese mitten crab (Eriocheir sinensis) as subjects to investigate the toxic effects on histopathology, oxidative stress, apoptosis and microbiota of hepatopancreas under environment-relevant (0.5 and 5 μg/L), and extreme concentrations (50 μg/L) of FF. Our results revealed that the damage of hepatopancreas tissue structure caused by FF exposure in a dose-and time-dependent manner. Combined with the increased expression of apoptosis-related genes (Caspase 3, Caspase 8, p53, Bax and Bcl-2) at mRNA and protein levels, activation of catalase (CAT) and superoxide dismutase (SOD), and malondialdehyde (MDA) accumulation, FF exposure also induced oxidative stress, and apoptosis in hepatopancreas. Interestingly, 7 days exposure triggered more pronounced toxic effect in crabs than 14 days under environment-relevant FF concentration. Integrated biomarker response version 2 (IBRv2) index indicated that 14 days FF exposure under extreme concentration has serious toxicity effect on crabs. Furthermore, 14 days exposure to FF changed the diversity and composition of hepatopancreas microbiota leading remarkable increase of pathogenic microorganism Spirochaetes following exposure to 50 μg/L of FF. Taken together, our study explained potential mechanism of FF toxicity on hepatopancreas of crustaceans, and provided a reference for the concentration of FF to be used in culture of Chinese mitten crab.

Violative chemical residues in edible tissues from food-producing animals are of global public health concern. Great efforts have been made to develop physiologically based pharmacokinetic (PBPK) models for estimating withdrawal intervals (WDIs) for extralabel prescribed drugs in food animals. Existing models are insufficient to address the food safety concern as these models are either limited to 1 specific drug or difficult to be used by non-modelers. This study aimed to develop a user-friendly generic PBPK platform that can predict tissue residues and estimate WDIs for multiple drugs including flunixin, florfenicol, and penicillin G in cattle and swine. Mechanism-based in silico methods were used to predict tissue/plasma partition coefficients and the models were calibrated and evaluated with pharmacokinetic data from Food Animal Residue Avoidance Databank (FARAD). Results showed that model predictions were, in general, within a 2-fold factor of experimental data for all 3 drugs in both species. Following extralabel administration and respective U.S. FDA-approved tolerances, predicted WDIs for both cattle and swine were close to or slightly longer than FDA-approved label withdrawal times (eg, predicted 8, 28, and 7 days vs labeled 4, 28, and 4 days for flunixin, florfenicol, and penicillin G in cattle, respectively). The final model was converted to a web-based interactive generic PBPK platform. This PBPK platform serves as a user-friendly quantitative tool for real-time predictions of WDIs for flunixin, florfenicol, and penicillin G following FDA-approved label or extralabel use in both cattle and swine, and provides a basis for extrapolating to other drugs and species.

BACKGROUND: Stenotrophomonas maltophilia (S.M.) is a Gram-negative bacillus, naturally resistant to cephalosporins and carbapenems, which can colonize different sites and may be responsible for serious infections for which treatment is a real challenge. We report 2 cases of nosocomial S.M. infection in 2 hospitalized newborns in the neonatal intensive care unit. CASE 1: A 3-day-old newborn presented with infection beginning in the respiratory system, treated with ciprofloxacin, and complicated by septicemia, resulting in death. CASE 2: An 11-day-old newborn presented with brain S.M. suppuration: empyema and multiple abscesses were treated successfully with the combination of amikacin and chloramphenicol with good progression in the short and medium terms.
CONCLUSIONS: Some epidemiological studies report that S.M. is the second Gram-negative bacillus responsible for nosocomial infection after Klebsiella pneumoniae. While the respiratory location of the bacterium is typical, cerebral parenchyma damage is rare in the newborn. The treatment remains very delicate and difficult because of this bacterium\'s drug multiresistance.
CONCLUSIONS: These 2 cases of infection caused by S.M. including respiratory tract infection with bacteremia and cerebral suppuration in newborns have broadened the spectrum of diseases caused by this organism and are a reminder of the emergence of this organism and its natural resistance to several antibiotics.

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The authors report ten cases of drug induced lung diseases, complicated by respiratory failure of whom five were attributed to cytotoxic drugs and five to non cytotoxic drugs. The drug induced lung disease presented as acute respiratory distress syndrome in two cases, alveolar interstitial lung disease in three cases, purely interstitial in five cases. There was acute respiratory failure (ARF) in eight cases and chronic respiratory failure (CRF) in two cases. Among the five patients admitted for cytotoxic drug induced lung disease and ARF, four recovered and one died of diffuse destructive pulmonary fibrosis. Among the five patients having non cytotoxic drug induced lung disease, three were in ARF and recovered. The other two had CRF and died of diffuse pulmonary fibrosis. The diagnostic of drug induced lung disease was established in each case with the chronology of the clinical events, the exclusion of other possible causes of the lung disease and the evolution after removal of the incriminated drug. Broncho-alveolar lavage (BAL) had a major diagnostic value. It was contraindicated by respiratory failure in five cases. The predominant alveolar cell type was lymphocyte (four cases), eosinophil (three cases) and neutrophil (one case), BAL was realized with a provocation test and demonstrated the pathogenic role of cyclothiazide in one case. No specific information was given by histology. The prognosis did not seem to be linked to the severity of the initial clinical picture, or to the nature of the underlying neoplastic disorder, but to the degree and evolution of the pulmonary fibrosis.

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