zithromax and Salmonella-Infections--Animal

Several experimental models have been used in order to evaluate the in vivo efficacy of azithromycin against numerous human pathogenic bacteria and parasites, including comparison between azithromycin and other antibiotics belonging or not to the macrolide family. Using the experimental models, three major objectives can be distinguished: the comparative studies of the efficacy dose 50 (ED50) of azithromycin compared to other orally given antibiotics, the azithromycin efficacy in animal infected with intracellular multiplying micro-organisms, and the demonstration of the specific azithromycin accumulation in tissues in direct relationship with the local recruitment of phagocytic cells at the infectious foci. The ED50 of azithromycin has been compared with those of erythromycin or cefaclor in varying acute murine infections. Evidence was given of a similar efficacy for the three tested antibiotics. Nevertheless a marked advantage for azithromycin was observed in experimental local infections and with infections due to Gram-negative bacteria (Haemophilus influenzae, Branhamella catarrhalis). The second objective was to confirm in vivo the preferential efficacy of azithromycin in models using intracellular multiplying microorganisms, due to its great capacity to accumulate inside of professional phagocytes. Several models have been used, such as those performed with Listeria monocytogenes, Legionella pneumophila, S. typhimurium, Brucella melitensis, M. avium and C. trachomatis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Cefaclor; Disease Models, Animal; Erythromycin; Legionnaires' Disease; Listeriosis; Lung Diseases; Mice; Mycobacterium avium; Parasitemia; Salmonella Infections, Animal; Tuberculosis

Non-typhoidal Salmonella enterica (NTS) are diverse and important bacterial pathogens consisting of more than 2600 different serovars, with varying host-specificity. Here, we characterized the poultry-associated serovars in Israel, analysed their resistome and illuminated the molecular mechanisms underlying common multidrug resistance (MDR) patterns. We show that at least four serovars including Infantis, Muenchen, Newport and Virchow present a strong epidemiological association between their temporal trends in poultry and humans. Worrisomely, 60% from all of the poultry isolates tested (n = 188) were multidrug resistant, mediated by chromosomal SNPs and different mobile genetics elements. A novel streptomycin-azithromycin resistance island and previously uncharacterized versions of the mobilized Salmonella genomic island 1 (SGI1) were identified and characterized in S. Blockley and S. Kentucky isolates respectively. Moreover, we demonstrate that the acquisition of SGI1 does not impose fitness cost during growth under nutrient-limited conditions or in the context of Salmonella infection in the mouse model. Overall, our data emphasize the role of the poultry production as a pool of specific epidemic MDR strains and autonomous genetic elements, which confer resistance to heavy metals and medically relevant antibiotics. These are likely to disseminate to humans via the food chain and fuel the increasing global antibiotic resistance crisis.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Drug Resistance, Multiple, Bacterial; Genomic Islands; Humans; Interspersed Repetitive Sequences; Israel; Mice; Microbial Sensitivity Tests; Polymorphism, Single Nucleotide; Poultry; Salmonella enterica; Salmonella Infections, Animal; Streptomycin

We identified 20 to 22 resistance genes, carried in four incompatibility groups of plasmids, in each of five genetically closely related

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Chickens; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Multigene Family; Plasmids; Salmonella Infections, Animal; Salmonella typhimurium; Swine; Taiwan; Whole Genome Sequencing

Antimicrobials play a critical role in treating cases of invasive non-typhoidal salmonellosis (iNTS) and other diseases, but efficacy is hindered by resistant pathogens. Selection for phenotypical resistance may occur via several mechanisms. The current study aims to identify correlations that would allow indirect selection of increased resistance to ceftriaxone, ciprofloxacin and azithromycin to improve antimicrobial stewardship. These are medically important antibiotics for treating iNTS, but these resistances persist in non-Typhi Salmonella serotypes even though they are not licensed for use in US food animals. A set of 2875 Salmonella enterica isolates collected from animal sources by the National Antimicrobial Resistance Monitoring System were stratified in to 10 subpopulations based on serotype and host species. Collateral resistances in each subpopulation were estimated as network models of minimum inhibitory concentration partial correlations. Ceftriaxone sensitivity was correlated with other β-lactam resistances, and less commonly resistances to tetracycline, trimethoprim-sulfamethoxazole or kanamycin. Azithromycin resistance was frequently correlated with chloramphenicol resistance. Indirect selection for ciprofloxacin resistance via collateral selection appears unlikely. Density of the ACSSuT subgraph resistance aligned well with the phenotypical frequency. The current study identifies several important resistances in iNTS serotypes and further research is needed to identify the causative genetic correlations.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Ciprofloxacin; Drug Resistance, Bacterial; Linear Models; Meat; Phenotype; Salmonella enterica; Salmonella Infections, Animal; Selection, Genetic; United States

The present study shows that a sub-MIC of the macrolide antibiotic azithromycin (AZM) diminishes the virulence function of Salmonella enterica serovar Typhimurium. We first constructed an AZM-resistant strain (MS248) by introducing ermBC, an erythromycin ribosome methylase gene, into serovar Typhimurium. The MIC of AZM for MS248 exceeded 100 microg/ml. Second, we managed to determine the efficacy with which a sub-MIC of AZM reduced the virulence of MS248 in vitro. On the one hand, AZM (10 microg/ml) in the culture medium was unable to inhibit the total protein synthesis, growth rate, or survival within macrophages of MS248. On the other hand, AZM (10 microg/ml) reduced MS248's swarming and swimming motilities in addition to its invasive activity in Henle-407 cells. Electron micrographs revealed no flagellar filaments on the surface of MS248 after overnight growth in L broth supplemented with AZM (10 microg/ml). However, immunoblotting analysis showed that flagellin (FliC) was fully synthesized within the bacterial cells in the presence of AZM (10 microg/ml). In contrast, the same concentration of AZM reduced the export of FliC to the culture medium. These results indicate that a sub-MIC of AZM was able to affect the formation of flagellar filaments, specifically by reducing the amount of flagellin exported from bacterial cells, but it was not involved in suppressing the synthesis of flagellin. Unfortunately, AZM treatment was ineffective against murine salmonellosis caused by MS248.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Cell Line; Epithelial Cells; Female; Flagella; Flagellin; Humans; Intestines; Macrophages; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Movement; Salmonella Infections, Animal; Salmonella typhimurium

Azithromycin was compared with ciprofloxacin for the treatment of established intracellular infection with Salmonella typhimurium LT-2 in CF-1 mice. For studies of mortality, mice received five times the LD50 of organisms intraperitoneally and were given drugs intragastrically once daily for seven days. For studies of in-vivo antibacterial activity, splenic viable counts were measured in mice that had received 0.5 times the intraperitoneal LD50 and had been given drugs for three days. The MICs of azithromycin and ciprofloxacin, respectively, against LT-2 were 4.0 and 0.03 mg/L. The 50% protective doses of the drugs required to prevent mortality were azithromycin 24.7 mg/kg/day, and ciprofloxacin 30.2 mg/kg/day. Treatment with azithromycin and ciprofloxacin in doses of 25 and 100 mg/kg/day resulted in reduction of mean log10 cfu per spleen. Splenic concentrations of azithromycin up to 8 h after treatment exceeded its MIC against the LT-2 strain, whereas serum levels were less than the MIC. These results indicated that azithromycin given orally once daily was as effective as ciprofloxacin against established murine Salmonella infection and that the efficacy of azithromycin correlated with adequate tissue concentrations of antibiotic.

Topics: Animals; Azithromycin; Ciprofloxacin; Colony Count, Microbial; Erythromycin; Female; Mice; Microbial Sensitivity Tests; Salmonella Infections, Animal; Salmonella typhimurium; Spleen