Etiologic and epidemiologic analysis of bacterial infectious upper respiratory disease in Thoroughbred horses at the Seoul Race Park

Infectious upper respiratory disease (IURD) of Thoroughbred racehorses has been a frequent problem (29.6% of incidence) at the Seoul Race Park (Korea). Risk factors for IURD include the season with a high transfer rate (summer and fall), the stabling period (≤ 3 months), and age (2 to 3 years old), suggesting that the movement and new environment may have depressed the immune system of the horses and decreased their ability to respond properly to pathogens. The bacterial strains (n = 98) isolated from IURD horses included Pseudomonas spp., Escherichia coli, Staphylococcus spp., Streptococcus equi subsp. equi and zooepidemicus

Aminoglycoside Susceptibility Profiles of Enterobacter cloacae Isolates Harboring the aac(6')-Ib Gene

The aminoglycoside 6'-N-acetyltransferases of type Ib (aac(6')-Ib) gene confers resistance to amikacin, tobramycin, kanamycin, and netilmicin but not gentamicin. However, some isolates harboring this gene show reduced susceptibility to amikacin. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommends a revision of the phenotypic description for isolates harboring the aac(6')-Ib gene. In this study, we determined the aminoglycoside susceptibility profiles of 58 AAC(6')-Ib-producing Enterobacter cloacae isolates. On the basis of the CLSI and EUCAST breakpoints, a large proportion (84.5% and 55.2%, respectively) of these 58 isolates were found to be susceptible to amikacin. However, among the isolates that were shown to be anikacin-susceptible according to the CLSI and EUCAST breakpoints, only 30.6% and 18.8% isolates, respectively, could be considered to have intermediate resistance on the basis of the EUCAST expert rules. Further studies should be conducted to determine the aminoglycoside susceptibility profiles of aac(6')-Ib-harboring isolates from various geographic regions and to monitor the therapeutic efficacy of amikacin in infections caused by these isolates

Advances in standardization of laboratory measurement procedures: implications for measuring biomarkers of folate and vitamin B-12 status in NHANES1234

Population studies such as NHANES analyze large numbers of laboratory measurements and are often performed in different laboratories using different measurement procedures and over an extended period of time. Correct clinical and epidemiologic interpretations of the results depend on the accuracy of those measurements. Unfortunately, considerable variability has been observed among assays for folate, vitamin B-12, and related biomarkers. In the past few decades, the science of metrology has advanced considerably, with the development of improved primary reference measurement procedures and high-level reference materials, which can serve as the basis for accurate measurement. A rigorous approach has been established for making field methods traceable to the highest-level reference measurement procedures and reference materials. This article reviews some basic principles of metrology and describes their recent application to measurements of folate and vitamin B-12

Colistin-sparing regimens against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae isolates: Combination of tigecycline or doxycycline and gentamicin or amikacin

AbstractBackground/PurposeIn vitro studies of the combination of an aminoglycoside with tigecycline or doxycycline against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates are rarely published. The goal of this study was to evaluate the antibacterial activity of the combination regimens.MethodsThirteen genetically different KPC-producing K. pneumoniae isolates were randomly selected. Drug concentrations of amikacin, gentamicin, tigecycline, and doxycycline were adjusted to 1-, 1/2-, and 1/4-fold of respective minimum inhibitory concentrations (MICs). Each drug alone or the combinations of amikacin or gentamicin with tigecycline or doxycycline were tested by combination studies.ResultsTreatment with the 1× MIC concentration in combinations of amikacin or gentamicin and tigecycline or doxycycline for 24 hours resulted in bactericidal activity of 84–100% in the isolates. Treatment with 1/2× MIC combinations resulted in synergism of 69–100% in the isolates. Notably, doxycycline plus gentamicin or amikacin was synergistic for all tested isolates. However, bactericidal or synergistic effect was barely evident following 1/4× MIC combinations. There was no antagonism in any of the combination regimens.ConclusionEnhanced activity was noted following treatment with doxycycline combined with gentamicin or amikacin against KPC-producing K. pneumoniae isolates, warranting further in vitro and animal investigations before clinical application

Effects of Therapeutical and Reduced Levels of Antibiotics on the Fraction of Antibiotic-Resistant Strains of Escherichia coli

Development of antibiotic resistance in the microbiota of farm animals and spread of antibiotic-resistant bacteria in the agricultural sector not only threaten veterinary use of antibiotics, but jeopardize human health care as well. The effects of exposure to antibiotics on spread and development of antibiotic resistance in Escherichia coli from the chicken gut were studied. Groups of 15 pullets each were exposed under strictly controlled conditions to a 2-day course of amoxicillin, oxytetracycline, or enrofloxacin, added to the drinking water either at full therapeutic dose, 75% of that, or at the carry-over level of 2.5%. During treatment and for 12 days afterwards, the minimal inhibitory concentration (MIC) for the applied antibiotics of E. coli strains isolated from cloacal swabs was measured. The full therapeutic dose yielded the highest percentage of resistant strains during and immediately after exposure. After 12 days without antibiotics, only strains from chickens that were given amoxicillin were significantly more often resistant than the untreated control. Strains isolated from pullets exposed to carry-over concentrations were only for a few days more often resistant than those from the control. These results suggest that, if chickens must be treated with antibiotics, a short intensive therapy is preferable. Even short-term exposure to carry-over levels of antibiotics can be a risk for public health, as also under those circumstances some selection for resistance takes place

Repurposing drugs to fast-track therapeutic agents for the treatment of cryptococcosis

Many infectious diseases disproportionately affect people in the developing world. Cryptococcal meningitis is one of the most common mycoses in HIV-AIDS patients, with the highest burden of disease in sub-Saharan Africa. Current best treatment regimens still result in unacceptably high mortality rates, and more effective antifungal agents are needed urgently. Drug development is hampered by the difficulty of developing effective antifungal agents that are not also toxic to human cells, and by a reluctance among pharmaceutical companies to invest in drugs that cannot guarantee a high financial return. Drug repurposing, where existing drugs are screened for alternative activities, is becoming an attractive approach in antimicrobial discovery programs, and various compound libraries are now commercially available. As these drugs have already undergone extensive optimisation and passed regulatory hurdles this can fast-track their progress to market for new uses. This study screened the Screen-Well Enzo library of 640 compounds for candidates that phenotypically inhibited the growth of Cryptococcus deuterogattii. The anthelminthic agent flubendazole, and L-type calcium channel blockers nifedipine, nisoldipine and felodipine, appeared particularly promising and were tested in additional strains and species. Flubendazole was very active against all pathogenic Cryptococcus species, with minimum inhibitory concentrations of 0.039-0.156 μg/mL, and was equally effective against isolates that were resistant to fluconazole. While nifedipine, nisoldipine and felodipine all inhibited Cryptococcus, nisoldipine was also effective against Candida, Saccharomyces and Aspergillus. This study validates repurposing as a rapid approach for finding new agents to treat neglected infectious diseases