Nicolás Javier Litterio

Background/Objectives: The expansion of intensive swine production in Córdoba, Argentina, underscores the need to assess the risks associated with antimicrobial (AM) use, whose extensive application has driven antimicrobial resistance, a major global threat within the One Health framework. This study aimed to characterize AM use practices and evaluate the epidemiological resistance profiles (non-wild-type phenotypes, NWT) of commensal Escherichia coli of fecal origin from swine farms, using epidemiological cut-off values (ECOFFs) as a surveillance criterion. Methods: An observational cross-sectional study was conducted in 19 farrow-to-finish farms in Córdoba during 2023. Information on AM use (prophylaxis, metaphylaxis, treatment) across production categories was collected. A total of 437 E. coli isolates were obtained from fecal samples, and minimum inhibitory concentrations (MICs) were determined for 10 AMs of critical importance for human and animal health. NWT phenotypes were classified according to EUCAST ECOFFs, and multidrug resistance (MDR) was assessed. Results: AM use was frequent and predominantly prophylactic (89.5% of farms), mainly through mass medication (66.3%), with macrolides and amoxicillin being the most commonly administered AMs. NWT proportions were extremely high (90–92%) for ampicillin, tetracyclines, and chloramphenicol and substantial for ciprofloxacin (50.6%), sulfamethoxazole (68.2%), and trimethoprim (44.9%). Extended-spectrum β-lactamase (ESBL)-producing phenotypes were detected. Alarmingly, 92% of isolates were classified as MDR E. coli, with homogeneous distribution across production categories. Conclusions: Findings reveal intensive and largely empirical AM use that has consolidated a stable intestinal resistome in the swine population. High MDR levels, even in categories with limited direct AM exposure or involving banned compounds, suggest that co-selection and horizontal gene transfer are key drivers of resistance. This scenario highlights the urgent need to strengthen integrated surveillance and promote prudent AM use strategies under the One Health approach to preserve therapeutic efficacy.

La diarrea posdestete (DPD) es un importante problema sanitario y económico en la producción porcina, donde Escherichia coli enterotoxigénica (ETEC) constituye uno de los principales agentes causales, provocando diarrea y retraso en el crecimiento, lo que conlleva un mayor uso de antimicrobianos y, en consecuencia, un incremento del riesgo de resistencia bacteriana. El objetivo de este estudio fue aislar cepas de E. coli a partir de muestras fecales de lechones con DPD en granjas de la provincia de Córdoba, Argentina, describir su perfil de resistencia a antimicrobianos de importancia crítica en salud pública y/o animal, y realizar su caracterización genotípica. Se recolectaron 69 muestras de hisopado rectal en seis establecimientos, con una tasa de aislamiento de E. coli del 97%. Se observó un perfil de resistencia preocupante, con altos niveles frente a betalactámicos (98,5%), fenicoles (88%), tetraciclinas (86,6%) y aminoglucósidos (34,3%). Además, 62 cepas (92,5%) fueron clasificadas como multirresistentes. De los 67 aislamientos obtenidos, el 70% correspondió a cepas ETEC, con alta prevalencia de los genes estII (74,5%) y estI (63,8%), asociados a la producción de toxinas. También se detectaron genes de adhesión como fedA (21,3%), faeG (14,9%), aidA (25,5%) y astA (14,9%). Estos resultados evidencian la fuerte presión de selección ejercida sobre las poblaciones bacterianas en los sistemas productivos, favoreciendo la persistencia y diseminación de cepas multirresistentes, y subrayan la necesidad de implementar medidas de control más estrictas para reducir su propagación en la producción porcina, con implicancias directas para la salud pública y bajo el enfoque de Una Salud.

La creciente presencia de aves silvestres, especialmente palomas, en áreas urbanas ha suscitado preocupaciones sobre su impacto en la salud pública, dado que pueden actuar como vectores de bacterias que poseen genes de resistencia a los antimicrobianos y de patógenos zoonóticos. Este estudio se centró en el aislamiento, identificación y evaluación del perfil de resistencia de Escherichia coli en materia fecal de aves silvestres en plazas recreativas infantiles de Córdoba, Argentina. Se recolectaron 14 muestras de materia fecal, de las cuales se aislaron seis cepas de Escherichia coli. Se observó un 67% de cepas resistentes al florfenicol, un 50% a enrofloxacina y gentamicina, un 33% a estreptomicina, tetraciclina y trimetoprim-sulfametoxazol, y un 16% a ceftiofur. Además, el 50% de las cepas fueron resistentes a más de un antimicrobiano, y el 33% resultaron ser multirresistentes. La presencia del gen eaeA, relacionado con cepas patógenas, se confirmó en las seis cepas aisladas. Estos hallazgos sugieren que la materia fecal de aves silvestres en plazas de Córdoba podría representar un riesgo zoonótico, especialmente para los niños que utilizan estos espacios.

Background: The personalization of medication through 3D printing enables the development of capsular devices (CDs) tailored to patient-specific needs. This study aimed to evaluate the stability and in vivo performance of 3D-printed polyvinyl alcohol (PVA) CDs with 0.4 and 0.9 mm width wall thicknesses (WT) compared to traditional hard gelatin capsules (HGCs). Methods: Capsules were tested for swelling, erosion, adhesion, water sorption, and in vitro disintegration. Additionally, the release of the model drug (losartan potassium) from CDs was evaluated. In vivo capsule opening times were assessed in dogs using X-ray imaging. Stability studies were conducted under natural (25 ± 2 °C, 60 ± 5% RH) and accelerated (40 ± 2 °C, 75 ± 5% RH) storage conditions. Results: CDs with 0.4 mm WT (CD–0–0.4) exhibited higher swelling and erosion, lower adhesion, and faster disintegration, leading to a more immediate drug release, comparable to HGCs. A strong correlation was found between in vitro and in vivo disintegration behavior. Water sorption tests revealed lower moisture affinity for PVA CDs compared to HGC. Stability studies showed that CD–0–0.4 retained its physical and chemical properties. Instead, CDs with 0.9 mm WT (CD–0–0.9) were sensitive to storage, particularly under accelerated aging, which affected their integrity and release profile. Conclusions: These findings highlight the potential of PVA-CDs, especially the 0.4 mm design, as a promising and stable alternative for compounding pharmacy applications, offering an effective platform for personalized oral drug delivery.

Niclosamide (NICLO) is a recognized antiparasitic drug being repositioned for Helicobacter pylori. The present work aimed to formulate NICLO nanocrystals (NICLO-NCRs) to produce a higher dissolution rate of the active ingredient and to incorporate these nanosystems into a floating solid dosage form to release them into the stomach slowly. For this purpose, NICLO-NCRs were produced by wet-milling and included in a floating Gelucire l3D printed tablet by semi-solid extrusion, applying the Melting solidification printing process (MESO-PP) methodology. The results obtained in TGA, DSC, XRD and FT-IR analysis showed no physicochemical interactions or modifications in the crystallinity of NICLO-NCR after inclusion in Gelucire 50/13 ink. This method allowed the incorporation of NICLO-NCRs in a concentration of up to 25% w/w. It achieved a controlled release of NCRs in a simulated gastric medium. Moreover, the presence of NICLO-NCRs after redispersion of the printlets was observed by STEM. Additionally, no effects on the cell viability of the NCRs were demonstrated in the GES-1 cell line. Finally, gastroretention was demonstrated for 180 min in dogs. These findings show the potential of the MESO-PP technique in obtaining slow-release gastro-retentive oral solid dosage forms loaded with nanocrystals of a poorly soluble drug, an ideal system for treating gastric pathologies such as H. pylori.

Coagulase-negative staphylococci are main pathogens that produce goat mastitis. Marbofloxacin is a third-generation fluoroquinolone approved for treat mastitis in animals. The objectives of this study were: (i) to determine the pharmacokinetics of marbofloxacin (10 mg/kg/24 h) in serum and milk administered intramuscularly for five days in goats with mastitis induced by coagulase-negative staphylococci; (ii) to characterize the concentration–effect relationship of marbofloxacin against coagulase-negative staphylococci in Mueller Hinton broth and goat milk; (iii) to determine AUC/MIC cutoff values of marbofloxacin, and (iv) to perform a PK/PD analysis to evaluate the efficacy of the dose regimen for the treatment of goat mastitis produced by coagulase-negative staphylococci. Marbofloxacin presented context-sensitive pharmacokinetics, influenced by the evolution of the disease, which decreased marbofloxacin disposition in serum and milk. Marbofloxacin showed a median (95% CI) fAUC/MIC values for MIC of 0.4 and 0.8 µg/mL of 26.66 (22.26–36.64) and 32.28 (26.57–48.35) related with −2 log₁₀CFU/mL reduction; and 32.26 (24.81–81.50) and 41.39 (29.38–128.01) for −3 log₁₀CFU/mL reduction in Mueller Hinton broth. For milk, −2 log₁₀CFU/mL reduction was achieved with 41.48 (35.29–58.73) and 51.91 (39.09–131.63), and −3 log₁₀CFU/mL reduction with 51.04 (41.6–82.1) and 65.65 (46.68–210.16). The proposed dose regimen was adequate for the treatment of goat mastitis produced by coagulase-negative staphylococci, resulting in microbiological and clinical cure of all animals. The animal model used in this study provided important pharmacokinetic information about the effect of the infection on the pharmacokinetics of marbofloxacin. Pharmacodynamic modeling showed that fAUC/MIC cutoff values were higher in goat milk compared with Mueller Hinton broth.

Cefquinome is a fourth‐generation cephalosporin that is used empirically in goats. Different physiologic factors like pregnancy or lactation could determine the pharmacokinetic behavior of drugs in the organism. The objectives of this study are to (a) compare the pharmacokinetics of cefquinome after intravenous and intramuscular administration in adult nonpregnant (n = 6), pregnant (n = 6), and lactating goats (n = 6), at a dose of 2 mg/kg, with rich sampling by nonlinear mixed‐effects modeling, (b) conduct a pharmacokinetic/pharmacodynamic analysis to evaluate the efficacy of the recommended posology in goats with different physiological states, and (c) determine the optimal posology that achieve a PTA value ≥ 90%, taking into account a T > MIC ≥ 60% of a MIC value ≤ 0.25 µg/ml, in the different subpopulations of goats for both routes. Gestation significantly increased Ka and V1, while reduced F0, Cl, and Q. On the other hand, lactation significantly increased V1 and reduced Tk0. Cefquinome concentrations achieved in placental cotyledon, amniotic fluid, and fetal serum indicate a minimal penetration across the placental barrier. Moreover, milk penetration of cefquinome was minimal. The total body clearance of cefquinome for goats was 0.29 L kg⁻¹ hr⁻¹, that is apparently higher than the reported for cows (0.13 L kg⁻¹ hr⁻¹) and pigs (0.16 L kg⁻¹ hr⁻¹). So, the optimal dose regimen for cefquinome after intravenous and intramuscular administration required higher dose and frequency of administration compared with recommendations for cows or pigs. Therefore, 2 mg kg⁻¹ 8 hr⁻¹ and 5 mg kg⁻¹ 12 hr⁻¹ could be used for IV and IM routes, respectively, for the treatment of respiratory infections caused by P. multocida and M. haemolytica, but only 5 mg kg⁻¹ 12 hr⁻¹ by both routes should be recommended for Escherichia coli infections.