In vitro activity of ceftazidime-avibactam against clinical isolates of Enterobacterales and Pseudomonas aeruginosa from sub-Saharan Africa: ATLAS Global Surveillance Program 2017-2021.

OBJECTIVES: To report the in vitro susceptibility of Enterobacterales (n = 3905) and Pseudomonas aeruginosa (n = 1,109) isolates, collected from patients in sub-Saharan Africa (four countries) in 2017-2021, to a panel of 10 antimicrobial agents with a focus on ceftazidime-avibactam activity against resistant phenotypes and ß-lactamase carriers. METHODS: MICs were determined by CLSI broth microdilution and interpreted using both 2022 CLSI and EUCAST breakpoints. ß-lactamase genes were identified in select ß-lactam-nonsusceptible isolate subsets using multiplex PCR assays. RESULTS: Among Enterobacterales, 96.2% of all isolates were ceftazidime-avibactam-susceptible (MIC90, 0.5 µg/mL), including all serine carbapenemase-positive (n = 127), 99.6% of ESBL-positive, carbapenemase-negative (n = 730), 91.9% of multidrug resistant (MDR; n = 1817), and 42.7% of DTR (difficult-to-treat resistance; n = 171) isolates. Metallo-ß-lactamase (MBL) genes were identified in most (n = 136; 91.2%) ceftazidime-avibactam-resistant isolates (3.5% of all Enterobacterales isolates). Ceftazidime-avibactam percent susceptible values ranged from 99.5% (Klebsiella species other than Klebsiella pneumoniae) to 92.5% (K. pneumoniae) for the various Enterobacterial taxa examined. Greater than 90% of Enterobacterales isolates from each country (Cameroon, Ivory Coast, Nigeria, South Africa) were ceftazidime-avibactam-susceptible. Among P. aeruginosa, 88.9% of all isolates were ceftazidime-avibactam-susceptible (MIC90, 16 µg/mL). Most (88.5%) MBL-negative, meropenem-resistant (n = 78), 68.1% of MDR (n = 385), and 19.2% of DTR isolates (n = 99) were ceftazidime-avibactam-susceptible. MBL genes were identified in 43.1% of ceftazidime-avibactam-resistant isolates (n = 53; 4.8% of all P. aeruginosa isolates). Country-specific ceftazidime-avibactam percent susceptible values for P. aeruginosa ranged from 94.1% (Cameroon) to 76.2% (Nigeria). CONCLUSION: Reference in vitro antimicrobial susceptibility testing demonstrated that most recent Enterobacterales (96%) and P. aeruginosa (89%) clinical isolates from four sub-Saharan African countries were ceftazidime-avibactam susceptible.

ß-sitosterol as an alternative to oxytetracycline: Effect on growth performance, feed intake and utilization efficiency and viscera macromorphometry of Cobb 500 broiler chickens.

Antibiotics are used to fortify broiler chicken feeds as growth promoters. Chronic antibiotic use pollutes the environment and causes the development of antibiotic resistance. Natural alternatives that mimic the properties of antibiotics, without causing health and environmental challenges are required. ß-sitosterol has antimicrobial, antioxidant, digestive and immune system modulating and growth stimulating activities. We evaluated its potential to replace oxytetracycline as a growth-promoter in broiler chicken feeds. Two hundred and forty, one-day-old Cobb 500 broiler chicks were randomly allocated to four diets where ß-sitosterol replaced oxytetracycline at 0 mg/kg (control; fortified with 50 mg/kg oxytetracycline), 500 mg/kg, 1000 mg/kg and 1500 mg/kg (w/w) feed and fed for 6 weeks: 2 weeks for each growth phase. Each diet was replicated thrice with 20 chicks per replicate. Initial, weekly and terminal body mass (TBM) and daily feed intake (FI) were measured. Body mass gain (BMG), average daily gain (ADG) and feed conversion ratio were computed. Terminally, the chickens were fasted for 4 h then slaughtered and dressed. Gastrointestinal tract (GIT) and GIT accessory viscera masses and small and large intestine lengths were measured. Dietary fortification with ß-sitosterol had similar effects (P > 0.05) to oxytetracycline on the chickens' TBM, BMG, ADG, FI and utilisation efficiency and GIT organ macromorphometry. In conclusion, ß-sitosterol can replace oxytetracycline in Cobb 500 broiler chicken feeds without compromising growth performance, feed intake and utilisation efficiency and GIT organ growth and development.

Neonatal Oral Administration of Chrysin Prevents Long-Term Development of Non-Alcoholic Fatty Liver Disease in a Sexually Dimorphic Manner in Fructose Nurtured Sprague Dawley Rats.

High-fructose diets are linked with the development of non-alcoholic fatty liver disease (NAFLD), the management of which is a burden to society. Interventions with phytochemicals in the early postnatal period may prevent fructose-induced NAFLD later in adulthood. We investigated the protective potential of chrysin against fructose-induced NAFLD. Four-day-old male and female suckling Sprague Dawley rats (N = 112) were randomly grouped and orally gavaged daily with distilled water (negative Control-Cn + W), chrysin(Chr-100 mg/kg), fructose-solution (Fr-20% w/v), and Chr + Fr between postnatal day (PND) 4 and 21 and then weaned onto normal rat chow and plain drinking water to PND 55. From PND 56 to 130, half of the rats continued on plain water, and the rest had Fr as drinking fluid. Terminally, the liver tissue was collected, and the lipid content was determined and histologically assessed for NAFLD. Dietary Fr induced an increased hepatic lipid content (p = 0.0001 vs. Cn + W) both sexes, and it was only attenuated by neonatal Chr in female rats (p < 0.05). Histologically, there was increased microvesicular steatosis (p = 0.0001 vs. Cn + W) in both sexes, and it was prevented by neonatal Chr (p > 0.05). Fr caused macrovesicular steatosis (p = 0.01 vs. Cn + W) in females only, and chrysin did not prevent it (p > 0.05). Fr induced hepatocellular hypertrophy, and inflammation was observed in females only (p = 0.01 vs. Cn + W), and this was prevented by Chr (p > 0.05). The collagen area fraction was increased by Fr (p = 0.02 (males) and p = 0.04 (females) vs. Cn + W, respectively; however, chrysin did not prevent this (p > 0.05). Neonatal chrysin prevented some of the deleterious effects of the high-fructose diet on the liver, suggesting that chrysin should be further explored as a strategic prophylactic neonatal intervention against high-fructose-diet-induced NAFLD.

Neonatal administration of zingerone prevents the subsequent development of high dietary fructose-induced early features of nephropathy in rats.

Excessive consumption of fructose-rich diets in early life stages increases the risk for developing nephropathy in adulthood. We investigated the potential preventive effects of neonatally administered zingerone on the development of dietary fructose-induced nephropathy. Four-day-old suckling male and female rat pups were orally gavaged (10 ml/kg) with: distilled water (Con group), 20% fructose solution (Fru group), 20% fructose solution + 40 mg/kg zingerone in distilled water (ZFru group), or 40 mg/kg of zingerone (Zgr group) for 14 days. Thereafter, Con and Zgr groups continued on plain drinking water while Fru and ZFru groups drank 20% fructose solution ad libitum for 10 weeks. The Fru group had significantly increased plasma concentration of the renal injury marker kidney injury molecule one (KIM-1) and decreased glomerular urinary space area compared to the controls in both sexes (p < 0.05). These alterations were prevented by neonatally administered zingerone. Zingerone administration neonatally is a potential prophylaxis for longterm high-fructose diet-induced nephropathy.

ß-Sitosterol mitigates the development of high-fructose diet-induced nonalcoholic fatty liver disease in growing male Sprague-Dawley rats.

Fructose contributes to the development of nonalcoholic fatty liver disease (NAFLD). ß-Sitosterol (Bst), a naturally occurring phytosterol, has antihyperlipidaemic and hepatoprotective properties. This study interrogated the potential protective effect of ß-sitosterol against NAFLD in growing rats fed a high-fructose diet, modelling children fed obesogenic diets. Forty-four 21 day old male rat pups were randomly allocated to and administered the following treatments for 12 weeks: group I, standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II, SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III, SRC + FS + 100 mg/kg fenofibrate in a gelatine cube; group IV, SRC + FS + 20 mg/kg ß-sitosterol gelatine cube (Bst); group V, SRC + PW + Bst. Terminally, the livers were dissected out, weighed, total liver lipid content determined, and histological analyses done. Harvested plasma was used to determine the surrogate biomarkers of liver function. The high-fructose diet caused increased (p < 0.05) hepatic lipid (total) accretion (>10% liver mass), micro- and macrovesicular hepatic steatosis, and hepatic inflammation. ß-Sitosterol and fenofibrate prevented the high-fructose diet-induced macrovesicular steatosis and prevented the progression of NAFLD to steatohepatitis. ß-Sitosterol can prospectively be used to mitigate diet-induced NAFLD.

ß-Sitosterol Shows Potential to Protect Against the Development of High-Fructose Diet-Induced Metabolic Dysfunction in Female Rats.

Metabolic syndrome (MetS) is a combination of risk factors that include insulin resistance, obesity, dyslipidemia, and hypertension. The consumption of high-fructose diets contributes to the development of MetS. ß-sitosterol a naturally occurring phytosterol possesses antiobesogenic and antidiabetic effects. This study evaluated the potential protective effect of ß-sitosterol against the development of metabolic dysfunction in growing female rats fed a high-fructose diet, mimicking children fed obesogenic diets. Thirty-five 21-day-old female Sprague Dawley rat pups were randomly allocated to and administered the following treatments: group 1-standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group 2-SRC + 20% w/w fructose solution (FS) as drinking fluid + PC; group 3-SRC + FS + 100 mg/kg fenofibrate in gelatine cubes; group 4-SRC + FS + 20 mg/kg ß-sitosterol gelatine cube (Bst); and group 5-SRC + PW + Bst. Following 12 weeks of feeding, the rats were fasted overnight, weighed, and then euthanized. Plasma cholesterol, insulin, glucose, triglyceride, and adiponectin concentrations were determined. Visceral fat was dissected out and weighed. The high-fructose diet increased (P < .05) visceral adiposity and plasma triglyceride concentration but decreased (P < .05) plasma adiponectin concentration. ß-sitosterol prevented the high-fructose diet-induced visceral obesity, hypertriglyceridemia, and hypoadiponectinemia. ß-sitosterol alone increased plasma adiponectin concentration and reduced plasma insulin concentration and homeostatic model assessment index. In conclusion, ß-sitosterol could be potentially used to prevent high-fructose diet-induced metabolic dysfunction.

Effect of crude Moringa oleifera Lam. seed extract on the blood markers of metabolic syndrome in high-fructose diet-fed growing Sprague-Dawley rats.

Background Moringa oleifera seed has anti-diabetic and anti-obesogenic properties. This study interrogated the effect of crude hydroethanolic M. oleifera seed extract on the blood markers of metabolic syndrome (MetS) in high-fructose diet fed growing Sprague-Dawley rats. Methods Sixty 21-day old female and male Sprague-Dawley rat pups were randomly allocated to and administered one of the following treatment regimens daily for twelve weeks: group I - plain drinking water (PW)+plain gelatine cube (PC), group II - 20% (w/v) fructose solution (FS)+PC, group III - FS+100 mg/kg body mass fenofibrate in gelatine cube (FN), group IV - FS+low dose (50 mg/kg body mass) of M. oleifera in gelatine cube (LMol) and group V - FS+high dose (500 mg/kg body mass) of M. oleifera in gelatine cube (HMol). The rats in each treatment regimen had ad libitum access to a standard rat chow. After the 12-week trial, the rats were subjected to an oral glucose tolerance test and then euthanised 48 h later. Blood was collected. Plasma triglyceride, cholesterol and insulin concentration were determined. HOMA-IR was then computed. Results The high-fructose diet increased (p<0.05) plasma insulin concentration and HOMA-IR in female rats only. It increased plasma triglyceride concentration in both female and male rats and plasma cholesterol concentration in male rats only. The crude hydroethanolic M. oleifera seed extract prevented the high-fructose diet-induced metabolic derangements in male and female rats. Conclusion Crude hydroethanolic M. oleifera seed extract can potentially be used as a prophylactic intervention for diet-induced MetS in children.

Terminalia Sericea aqueous leaf extract protects growing wistar rats against fructose-induced fatty liver disease.

Background Terminalia sericea (T. sericea) is traditionally used to treat stomach ailments, infections, hypertension and diabetes mellitus. Previous in vitro studies have reported that T. sericea has lipolytic properties. This study interrogated the effects of T. sericea on linear growth, development of fatty liver disease, viscera morphometry and health of growing rats fed a 12% fructose solution (FS). Methods Thirty 21-day old male Wistar rat pups were randomly allocated to five treatments: group I - plain gelatine cubes (PGC) + plain tap water (PW), group II - 12% FS + PGC, group III - gelatine cubes containing fenofibrate (Feno) at a dose of 100 mg/kg body + FS, group IV - gelatine cubes containing the low dose (100 mg/kg body mass per day) of the T. sericea extract (TsL) + FS, group V - gelatine cubes containing the high dose (400 mg/kg body mass per day) of the T. sericea extract (TsH) + FS. Following 12 weeks of feeding, the rats were fasted overnight, euthanized and plasma and viscera harvested for analysis. Results Consumption of fructose resulted in significantly increased (p<0.05) liver lipid content and caused macrovesicular steatosis. The T. sericea extracts at 400 mg/kg per day suppressed the fructose-induced liver lipid accumulation and macrovesicular steatosis similarly to 100 mg/kg per day of Feno. Conclusions These findings suggest that the aqueous T. sericea leaf extract at 400 mg/kg per day could potentially protect against fructose-induced lipid accumulation as well as macrovesicular steatosis.

Insulinotropic Effect of S-Allyl Cysteine in Rat Pups.

S-Allyl cysteine (SAC) is found in garlic and has been reported to exert antidiabetic and antiobesity properties in drug-induced adult experimental models of metabolic dysfunction, but its potential beneficial effects in high-fructose diet neonatal rat models have not been determined. This study investigated the potential prophylactic effects of SAC in high-fructose diet fed suckling rat pups modelling human neonates fed a high-fructose diet. Four-day-old male (n=32) and female (n=32) Wistar rat pups, were randomly assigned to and administered the following treatment regimens daily for 15 days: group I, distilled water; group II, 20% fructose solution (FS); group III, SAC; group IV, SAC+FS. The pups' blood glucose, triglyceride, cholesterol, plasma leptin and insulin concentration, liver lipid content, and liver histology were determined at termination. In female rat pups, orally administered SAC prevented FS-induced hypoinsulinemia but significantly increased (P≤0.05) liver lipid content. Oral administration of SAC significantly increased (P≤0.05) plasma insulin concentration and homeostasis model assessment for insulin resistance in the male pups. The potential sexually dimorphic effects of SAC (insulinotropic effects in male pups and protection of female pups against fructose-induced hypoinsulinemia) suggest that SAC could be potentially exploited as an antidiabetic and insulinotropic agent. Caution should, however, be exercised in the use of SAC during suckling as it could result in excessive liver lipid accumulation and insulin resistance.

Fat absorption and deposition in Japanese quail (Coturnix coturnix japonica) fed a high fat diet.

Dietary fat contributes significantly to the energy requirements of poultry. Not all species are able to increase their absorptive capacity for fats in response to a high fat diet. The effects of a high fat diet (10% canola oil) on the lipid absorption and deposition in the liver, breast and thigh muscles of male and female Japanese quail were investigated. Thirty-eight Japanese quail (Coturnix coturnix japonica) were randomly divided into a high fat diet (HFD) and a standard diet (STD) group. The birds were fed the diets for seven weeks after which half of the birds were subjected to oral fat loading tests (OFLT) with plant oils containing long-chain and medium-chain triglycerides. The remaining birds were included for the lipid deposition measurements. Thereafter the birds were euthanised, blood samples were collected and liver, breast and thigh muscle lipid deposition was determined. Female quail on both diets had significantly higher plasma triglyceride concentrations (p < 0.05) compared with their male counterparts. No significant differences in plasma triglyceride concentrations were observed after the OFLTs. Female quail had significantly heavier liver masses compared with the males but there was no significant difference in the liver lipid content per gram liver mass. Female quail on the HFD had higher lipid content (p < 0.05) in the breast muscle compared with their male counterparts whilst male quail on the HFD had higher lipid content (p < 0.05) in the thigh muscle in comparison with both males and females on the standard diet. Dietary supplementation with 10% canola oil did not alter gastrointestinal tract lipid absorption, but it caused differences between the sexes in muscle lipid accumulation, the physiological significance of which requires further investigation.