Assessment the efficacy of some various treatment methods, in vitro and in vivo, against Aeromonas hydrophila infection in fish with regard to side effects and residues.

Aeromonas hydrophila is an opportunistic bacteria with an overwhelming impact on fish farming industry especially with upraising of drug resistant mutants. This study aimed to evaluate and compare the therapeutic and side effects of levofloxacin (LEV), chitosan-nanoparticles (CNPs), and fructooligosaccharides (FOS) in control of this infection in tilapia. A total of 160 Nile-tilapia divided into 8-groups; G1: negative-control, G2: infected-control, G3: non-infected-(levofloxacin (LEV) 10 mg/kg bwt), G4: non-infected-(chitosan-nanoparticles (CNPs) 1 g/kg ration), G5: non-infected-(fructooligosaccharides (FOS) 20 g/kg ration), G6: infected-LEV, G7: infected-CNPs and G8: infected-FOS for 7 days. MICs were (0.125 µg/ml and 1.25 mg/ml) for LEV and CNPs respectively. No mortalities or significant adverse effects were recorded in non-infected treated-groups while infected were (20%) LEV, (30%) CNPs, (40%) FOS and (70%) G2. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) decreased by LEV and CNPs than FOS while all increased total protein (TP) and albumin than G2. Malondialdehyde (MDA) significantly decreased and superoxide dismutase (SOD) and reduced glutathione (GSH) increased in all infected-treated groups than G2 in various degrees. Urea and creatinine descending order were FOS, LEV then CNPs decreased significantly than G2. LEV musculature residues, using HPLC, decreased gradually till the 5th day; 621.00 ± 0.66, 270.00 ± 0.48 then 64.00 ± 0.40, and 471.00 ± 0.79, 175.00 ± 0.52 ppb then not detected at 1st, 3rd, and 5th days of withdrawal in non-infected and infected groups respectively. Finally, LEV and CNPs were superior as bactericidal, decreasing mortalities and enzyme activities while CNPs and FOS increased performance, non-specific immunity, and antioxidant biomarkers.

Fight Against Antimicrobial Resistance: We Always Need New Antibacterials but for Right Bacteria.

Antimicrobial resistance in bacteria is frightening, especially resistance in Gram-negative Bacteria (GNB). In 2017, the World Health Organization (WHO) published a list of 12 bacteria that represent a threat to human health, and among these, a majority of GNB. Antibiotic resistance is a complex and relatively old phenomenon that is the consequence of several factors. The first factor is the vertiginous drop in research and development of new antibacterials. In fact, many companies simply stop this R&D activity. The finding is simple: there are enough antibiotics to treat the different types of infection that clinicians face. The second factor is the appearance and spread of resistant or even multidrug-resistant bacteria. For a long time, this situation remained rather confidential, almost anecdotal. It was not until the end of the 1980s that awareness emerged. It was the time of Vancomycin-Resistance Enterococci (VRE), and the threat of Vancomycin-Resistant MRSA (Methicillin-Resistant Staphylococcus aureus). After this, there has been renewed interest but only in anti-Gram positive antibacterials. Today, the threat is GNB, and we have no new molecules with innovative mechanism of action to fight effectively against these bugs. However, the war against antimicrobial resistance is not lost. We must continue the fight, which requires a better knowledge of the mechanisms of action of anti-infectious agents and concomitantly the mechanisms of resistance of infectious agents.

Assessment of Gill Pathological Responses in Yellowfin Sea Bream (Acanthopagrus Latus) Under Aeromonas Hydrophila Exposure.

Bacterial diseases in cultured fish are considered the main problem with aquaculture system in Iran. The gills are multifunctional organs responsible for respiration, osmoregulation, nitrogenous waste excretion, and acid-base balance. Moreover, they are very sensitive to water contamination. Aeromonas hydrophila (A. hydrophila) is an opportunist pathogen responsible for a wide range of diseases in different species of fish. The gill histological alterations were used to assess the effects of A. hydrophila exposure on yellowfin sea bream, Acanthopagrus latus (A. latus). In this regard, 90 A. latus were exposed to the concentrations of A. hydrophila (103 and 106 CFU/ml) for three weeks. The most histopathological alterations in the gill of the exposed fish included hypertrophy and hyperplasia of the epithelial cells, lamellar fusion, club shaping of gill lamellae, lifting of the epithelium and edema of lamellae with large sub-epithelial space, blood congestion, and hypertrophy and hyperplasia of the mucosal cells. The histopathological alterations were observed in the gill of fish exposed to higher levels of A. hydrophila (106 CFU/ml) consisted of aneurysm and hemorrhage with blood congestion. According to the obtained results of this study, A. hydrophila could cause severe histopathological changes in the gill of A. latus and decrease gas change capability in yellowfin sea bream. Furthermore, the findings of the present study suggested that histopathological changes of the gill provide helpful information about the environmental conditions and as particular biomarkers may help the evaluation of fish general health.

Attributable clinical and economic burden of carbapenem-non-susceptible Gram-negative infections in patients hospitalized with complicated urinary tract infections.

BACKGROUND: Gram-negative complicated urinary tract infections (cUTIs) can have serious consequences for patients and hospitals. AIM: To examine the clinical and economic burden attributable to Gram-negative carbapenem-non-susceptible (C-NS; resistant/intermediate) infections compared with carbapenem-susceptible (C-S) infections in 78 US hospitals. METHODS: All non-duplicate C-NS and C-S urine source isolates were analysed. A subset had principal diagnosis ICD-9-CM codes denoting cUTI. Collection time (<3 vs ≥3 days after admission) determined isolate classification as community or hospital onset. Mortality, 30-day re-admissions, length of stay (LOS), hospital cost and net gain/loss in US dollars were determined for C-NS and C-S cases, with the C-NS-attributable burden estimated through propensity score matching. Three subgroups with adequate patient numbers were analysed: cUTI principal diagnosis, community onset; other principal diagnosis, community onset; and other principal diagnosis, hospital onset. FINDINGS: The C-NS-attributable mortality risk was significantly higher (58%) for the other principal diagnosis, hospital-onset subgroup alone (odds ratio 1.58, 95% confidence interval 1.14-2.20; P < 0.01). The C-NS-attributable risk for 30-day re-admission ranged from 29% to 55% (all P < 0.05). The average attributable economic impact of C-NS was 1.1-3.9 additional days LOS (all P < 0.05), US$1512-10,403 additional total cost (all P < 0.001) and US$1582-11,848 net loss (all P < 0.01); overall burden and C-NS-attributable burden were greatest in the other principal diagnosis, hospital-onset subgroup. CONCLUSION: Greater clinical and economic burden was observed in propensity-score-matched patients with C-NS infections compared with C-S infections, regardless of whether cUTI was the principal diagnosis, and this burden was most severe in hospital-onset infections.

A Population and Developmental Pharmacokinetic Analysis To Evaluate and Optimize Cefotaxime Dosing Regimen in Neonates and Young Infants.

Cefotaxime is one of the most frequently prescribed antibiotics for the treatment of Gram-negative bacterial sepsis in neonates. However, the dosing regimens routinely used in clinical practice vary considerably. The objective of the present study was to conduct a population pharmacokinetic study of cefotaxime in neonates and young infants in order to evaluate and optimize the dosing regimen. An opportunistic sampling strategy combined with population pharmacokinetic analysis using NONMEM software was performed. Cefotaxime concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Developmental pharmacokinetics-pharmacodynamics, the microbiological pathogens, and safety aspects were taken into account to optimize the dose. The pharmacokinetic data from 100 neonates (gestational age [GA] range, 23 to 42 weeks) were modeled with an allometric two-compartment model with first-order elimination. The median values for clearance and the volume of distribution at steady state were 0.12 liter/h/kg of body weight and 0.64 liter/kg, respectively. The covariate analysis showed that current weight, GA, and postnatal age (PNA) had significant impacts on cefotaxime pharmacokinetics. Monte Carlo simulations demonstrated that the current dose recommendations underdosed older newborns. A model-based dosing regimen of 50 mg/kg twice a day to four times a day, according to GA and PNA, was established. The associated risk of overdose for the proposed dosing regimen was 0.01%. We determined the population pharmacokinetics of cefotaxime and established a model-based dosing regimen to optimize treatment for neonates and young infants.

[ANALYSIS OF MICROFLORA OF PLEURAL CAVITY IN PLEURAL EMPYEMA].

In the pleural empyema (PE) treatment, not depending on introduction of multiple operative procedures and the medicinal preparations application, some issues remain unsolved, including the infection agents verification, the most rapid bronchial fistula elimination and the lung volume restoration. The EP infection agents spectrum, their sensitivity to preparations were revealed, as well as the enhanced rate of the methicillin-resistant stamms (MRSA) and the microorganisms associations verification. A reduction of the infection agents sensitivity towards "simple" antibacterial preparations was established, so the physicians, treating PE, must prescribe "hard" antibiotics, what enhances its cost.

Extended-Infusion versus standard-infusion piperacillin-tazobactam for sepsis syndromes at a tertiary medical center.

Piperacillin-tazobactam (PTZ) is frequently used as empirical and targeted therapy for Gram-negative sepsis. Time-dependent killing properties of PTZ support the use of extended-infusion (EI) dosing; however, studies have shown inconsistent benefits of EI PTZ treatment on clinical outcomes. We performed a retrospective cohort study of adult patients who received EI PTZ treatment and historical controls who received standard-infusion (SI) PTZ treatment for presumed sepsis syndromes. Data on mortality rates, clinical outcomes, length of stay (LOS), and disease severity were obtained. A total of 843 patients (662 with EI treatment and 181 with SI treatment) were available for analysis. Baseline characteristics of the two groups were similar, except for fewer female patients receiving EI treatment. No significant differences between the EI and SI groups in inpatient mortality rates (10.9% versus 13.8%; P = 0.282), overall LOS (10 versus 12 days; P = 0.171), intensive care unit (ICU) LOS (7 versus 6 days; P = 0.061), or clinical failure rates (18.4% versus 19.9%; P = 0.756) were observed. However, the duration of PTZ therapy was shorter in the EI group (5 versus 6 days; P < 0.001). Among ICU patients, no significant differences in outcomes between the EI and SI groups were observed. Patients with urinary or intra-abdominal infections had lower mortality and clinical failure rates when receiving EI PTZ treatment. We did not observe significant differences in inpatient mortality rates, overall LOS, ICU LOS, or clinical failure rates between patients receiving EI PTZ treatment and patients receiving SI PTZ treatment. Patients receiving EI PTZ treatment had a shorter duration of PTZ therapy than did patients receiving SI treatment, and EI dosing may provide cost savings to hospitals.

Assessment of Aquaflor(®) , copper sulphate and potassium permanganate for control of Aeromonas hydrophila and Flavobacterium columnare infection in sunshine bass, Morone chrysops female × Morone saxatilis male.

Two experiments were conducted to test the effectiveness of different therapeutants against a mixed infection of Aeromonas hydrophila and Flavobacterium columnare in sunshine bass. Experiment 1 evaluated copper sulphate, florfenicol-medicated feed and potassium permanganate (KMnO(4) ) against a natural mixed infection. Experiment 2 further evaluated copper sulphate as a treatment to control an experimental mixed infection. In experiment 1, naturally infected untreated fish had the lowest final survival per cent, at 71%, while florfenicol-medicated feed at 15mgkg(-1) body weight for 10days or copper sulphate at 2.1mgL(-1) (1% of the total alkalinity) for 24h produced the highest final survivals, at 90% and 88%, respectively. The final survival of the naturally infected fish administered florfenicol-medicated feed was significantly different (P<0.1) from the untreated fish. The survival curves for the florfenicol and the copper sulphate at 2.1mgL(-1) were significantly improved from the untreated fish. In experiment 2, fish were challenged by waterborne exposure to A. hydrophila and F. columnare and either not treated or treated with copper sulphate at 2.1mgL(-1) . At the end of experiment 2, the per cent survival of the challenged fish treated with copper sulphate (99%) was significantly higher (P<0.05) than the non-treated (61%). The results illustrate clear benefit of florfenicol and copper sulphate against a mixed infection of A. hydrophila and F. columnare.

Deep tissue biopsy vs. superficial swab culture monitoring in the microbiological assessment of limb-threatening diabetic foot infection.

AIMS: The results of ulcer swabbing vs. deep tissue biopsy have been compared prospectively in 29 diabetic patients with limb-threatening foot infection, to investigate the effectiveness and reliability of each method, and to evaluate whether any of the two could be more suitable for the microbiological follow-up of severe lesions. METHODS: Microbiological samples were collected by using both methods at fixed intervals after therapy commencement (i.e. at day 0, 7, 14, and 30). Statistical comparison was performed between the results of each sampling procedure after the end of follow-up. RESULTS: At enrolment, the mean number of isolates per patient was 2.34 by swabbing and 2.07 by tissue biopsy sampling; the rate of isolation for anaerobes with the two methods was 35% and 25%, respectively; no statistical differences could be observed between the two procedures in terms of either species or frequency of isolation. Anaerobic species were never detected after the first 2 weeks of appropriate treatment, and those ulcers which were still active at day 30 yielded almost exclusively Gram-positive bacteria. At the end of follow-up, deep tissue cultures appeared to exhibit a higher diagnostic sensitivity with respect to swabs. CONCLUSIONS: Swabbing and deep tissue cultures appear to be equally reliable for the initial monitoring of antimicrobial treatment in severe diabetic foot infection. However, our experience seems to suggest that deep tissue might be more sensitive than swabbing for monitoring those isolates that have been selected for antibiotic resistance, i.e. those from ulcers that are still active after 30 days of treatment.