Search Results (33)

Background/Objectives: Staphylococcus aureus (S. aureus) intramammary infection remains a major global dairy problem due to its contagious nature, its ability to persist and colonize teat/skin and mucosal niches, and the often-limited bacteriological cure achieved with antimicrobial therapy. Beyond udder health, it is relevant to public health because it can enter raw milk chains and serve as a reservoir for antimicrobial resistance determinants that may circulate between dairy animals and humans. Methods: We assessed S. aureus’ ecology in raw ewe milk from 75 sheep farms in Epirus (Greece) by sampling clinically healthy controls (group A) and clinical mastitis cases pre-treatment (group B), followed by resampling at the first post-withdrawal milking after penicillin/streptomycin treatment (group C1—therapeutic protocol 1), oxytetracycline treatment (group C2—therapeutic protocol 2), or enrofloxacin treatment (group C3—therapeutic protocol 3). Results: S. aureus detection was high and comparable across groups (A 23.0%, B 22.0–30.0%, C 20.0–22.0%), and paired analyses showed no significant pre–post shifts in detection/burden within therapeutic protocols (all p > 0.05). Nevertheless, persistence remained evident. The chromosomal gene mecA was detected in S. aureus strains in all groups, ranging from 13.6% in controls to 54.5% post-withdrawal in group C1, and was also present in the pre-treatment group. In paired sampling animals, mecA was mostly stable, with rare emergence or loss. Across antibiotic classes, within-animal resistance transitions were generally uncommon and non-significant (p > 0.05); β-lactam resistance was fully stable (p = 1.00). Descriptively, resistance to protein synthesis inhibitors tended to decline after therapy in protocol 1 and protocol 3, while protocol 3 showed post-treatment gains in fluoroquinolone resistance. By contrast, virulence-associated phenotype traits shifted after therapy: enterotoxigenicity increased post-withdrawal (especially in the C3 group), Staphylococcal Enterotoxin A (SEA) and Staphylococcal Enterotoxin B (SEB) appeared only post-therapy, Staphylococcal Enterotoxin D (SED) increased significantly in paired isolates (p = 0.002), and strong biofilm adherence increased (in C3, p = 1.5 × 10⁻⁵). Conclusions: The detection of S. aureus after therapy suggests that one possibility is that antimicrobial exposure may select for, or otherwise reshape, the residual intramammary population, rather than reliably eliminating it—an outcome that remains clinically relevant for udder health. Moreover, the persistence of mecA/methicillin-resistant Staphylococcus aureus (MRSA)-compatible profiles indicates that milk released to the food chain after withdrawal compliance may still harbor S. aureus with enhanced preservation capacity and significant food safety relevance. Full article

Historically, methods to detect subclinical mastitis have been used to aid treatment decisions. The limitations of these tests have led to the exploration of the use of differential somatic cell count (DSCC). The objective of this study was to evaluate the relationship between DSCC and antibiotic success in subclinically infected cows. Cows were pre-screened to confirm an SCC ≥ 200,000 cells/mL and a positive bacterial culture. At enrollment, aseptic quarter milk samples were collected for culturing and evaluated using SCC, DSCC, the California Mastitis Test (CMT), and electrical conductivity. Enrolled quarters were treated with an intramammary antibiotic and resampled 7-, 14-, 28-, and 35-days post-treatment and retrospectively classified as “Cured” or failed to cure (Failed) based on a bacteriological cure. The overall cure rate was 51.5%. Pre-treatment SCC, total leukocyte count (TLC), neutrophils, and CMT were lower in Cured quarters compared to Failed. Meanwhile, macrophage percentage was greater in Cured quarters compared to Failed. No difference was found between lymphocyte percentage and conductivity. When evaluating the use of multiple threshold optimizations to predict cure outcome, TLC tended to have the highest ranking for the metric of interest; however, SCC tended to numerically perform as well in sensitivity and specificity outside of the optimized parameter. Full article

Background/Objectives: Staphylococcus (S.) aureus is a major pathogen causing bovine mastitis and is often refractory to antibiotic therapies due to virulence factors and resistance mechanisms. In this pilot study, the safety and efficacy of an intramammary phage cocktail, in naturally S. aureus-infected dairy cows, were investigated. Methods: The initial part of the study on farm 1 confirmed tolerability and safety, as there were no observed systemic side effects of treatment. The subsequent efficacy study on farm 2 included 23 with S. aureus infected udder quarters, which were randomly divided into a treatment group (n = 16) and a control group (n = 7). The quarters in the treatment group received five intramammary infusions of the phage cocktail at 12-h intervals. Results: This resulted in a bacteriological cure rate of 81.3% (13/16) for the treatment group, compared to 28.6% (2/7) in the control group (p = 0.026). Conclusions: These results indicate that phage therapy is well-tolerated and may be a promising alternative to antibiotics for treating S. aureus mastitis, although confirmation in larger-scale, multicenter studies is required. Full article

Background: Rifaximin is a non-aminoglycoside antibiotic utilized for the treatment of mastitis in cows, but its milk disposition kinetics, residue, and bacteriological status in lactating cow milk have hardly been reported. This study aimed to assess the milk disposition kinetics and residue of rifaximin in milk and to evaluate the bacteriological status in milk after intramammary treatment with rifaximin. Methods: An ultra-high-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) approach was developed to assess rifaximin concentrations in milk. Milk disposition kinetics parameters of rifaximin in cow milk were obtained by non-compartment model analysis. Rifaximin residues in milk were analyzed up to 108 h post-administration to estimate the withdrawal period. Clinically, the efficacy of Rifaximin Intramammary Infusion (Lactating Cow) was evaluated in mastitis cases caused by various pathogens and compared with lincomycin as the control drug, including clinical cure rate, bacteriological cure rate, and somatic cell count (SCC) at D21 post-treatment. Results: The C_max of rifaximin in milk was 54,273.3 ± 12,421.32 ng/mL, the area under the curve (AUC) was 340,731.8 ± 43,968.82 h⋅ng/mL, the T_1/2 was 5.57 ± 0.68 h, the mean resident time (MRT) was 7.3927 ± 1.34 h, and the area under the moment curve (AUMC) was 2,475,745 ± 230,305.1 h⋅h⋅ng/mL. Based on rifaximin residues in milk, the withdrawal period for cow milk was calculated to be 95.1 h. Clinically, Rifaximin Intramammary Infusion (Lactating Cow) demonstrated a clinical cure rate of 83.33% and a bacteriological cure rate of 76.67% in mastitis cases caused by various pathogens, with both rates being 10% higher than those of lincomycin. At D21 post-treatment, the rifaximin group had a significantly lower SCC than the lincomycin group (p < 0.05). Conclusions: Rifaximin exhibits favorable milk disposition kinetics, an acceptable withdrawal period of 95.1 h, and good clinical and bacteriological cure rates in bovine mastitis. These findings support rifaximin as a useful intramammary option and contribute to rational antimicrobial use and milk safety in dairy. Full article

Mastitis caused by Escherichia coli and Streptococcus uberis remains one of the leading causes of antimicrobial use in dairy cattle, contributing to resistance development and economic losses. This study evaluated the therapeutic potential of the natural flavonoid morin in clinical mastitis in dairy cows. The in vitro antimicrobial activity of morin (1–3% w/v) was assessed by disk diffusion, and the 3% formulation was selected for an in vivo field trial. Seventy-two Holstein–Friesian cows with mastitis caused by E. coli or S. uberis were randomly assigned to one of three intramammary treatments: 3% morin, phosphate-buffered saline, or an antibiotic, serving as a positive control. Somatic cell count (SCC) and clinical scores were monitored for seven days. In E. coli infections, morin significantly reduced somatic cell scores at 144 h and 168 h and improved clinical scores from 48 h onward, showing efficacy comparable to antibiotics. In S. uberis mastitis, morin induced clinical improvement at 96–168 h but resulted in slower and smaller SCC reduction than antibiotic control therapy. Phosphate-buffered saline produced no significant changes. These results indicate that morin exerts anti-inflammatory and supportive effects in bovine mastitis, particularly in Gram-negative infections, but is less effective against S. uberis. Further studies on pharmacokinetics, bacteriological cure rates, and optimized formulations are warranted to confirm its clinical utility. Full article

Leptospirosis, caused by Leptospira spp., affects multiple domestic species and can result in significant economic and public health impacts. This scoping review, conducted following the PRISMA 2020 guidelines, searched PubMed, SciELO, and Scopus for original studies that described complete therapeutic protocols (including dose, duration, and confirmed diagnosis) in dogs, cats, cattle, pigs, horses, sheep, and goats. Thirty-five studies met the criteria: 14 (40%) in cattle, 7 (20%) in swine, 2 (5.7%) in small ruminants, 7 (20%) in dogs and cats, and 5 (14.3%) in horses. In livestock, streptomycin monotherapy has predominated, demonstrating high efficacy against renal and genital carriers, but it faces regulatory restrictions in several countries. In companion animals, treatment often addressed acute cases using doxycycline and aminopenicillins, with frequent drug combinations. Horses were mainly treated with penicillin, alone or associated with other agents. Across species, protocols showed substantial heterogeneity, lack of harmonization, and limited evaluation of bacteriological cure, with most studies published before 2000. This scarcity of recent clinical trials reinforces the neglected status of animal leptospirosis. By compiling fragmented evidence, this review identifies converging practices that may serve as a preliminary consensus, highlights discrepancies and knowledge gaps, and provides an evidence-based framework to support the development of standardized, species-specific guidelines urgently needed in a One Health context. Full article

The rise in antimicrobial resistance and strict milk withdrawal regulations drive the search for safe, non-antibiotic intramammary therapies. This pilot field study focused on clinical parameters, including the somatic cell count (SCC) and the assessment of changes, as well as overall safety, which together enabled a prospective evaluation of whether the substance exerted any therapeutic effect. In this study, 48 Holstein–Friesian cows with naturally occurring clinical mastitis (somatic cell count > 400,000 cells/mL; single quarter) were randomized to receive either seven daily infusions of 10% pectin (n = 24) or two standard intramammary doses of a licensed multi-component antibiotic formulation (n = 24). The clinical severity scores (0–3) and SCC were monitored from 72 h before to 168 h after treatment initiation; the bacteriological cultures, milk TNF-α, milk yield, and blood hematology/biochemistry were also assessed. Both groups exhibited comparable and significant reductions in the mastitis scores and log₂-transformed SCC by 48 h post-treatment, with equivalent bacteriological cure rates and pathogen profiles (predominantly Streptococcus uberis, coagulase-negative staphylococci, and Escherichia coli) and no local irritation, systemic adverse effects, or alterations in the milk yield, TNF-α, or blood parameters. These findings indicate that intramammary pectin at a 10% concentration is safe and well tolerated and that it provides efficacy equivalent to standard antibiotic therapy, supporting its potential as an alternative mastitis treatment that avoids antibiotic residues and contributes to antimicrobial stewardship. Full article

Background/Objectives: This review aimed to compare the efficacy of antibiotic treatment vs. non-antibiotic treatment in mild and moderate clinical mastitis in lactating dairy cows, categorized by the causative pathogen. Methods: The initial systematic review plan, which resulted in only four relevant articles, was altered due to limited available studies and significant heterogeneity among them. Consequently, five additional articles, closely meeting our criteria with minor differences, were included to ensure comprehensive analysis, resulting in nine included articles. Due to these pragmatic constraints, this review represents a hybrid between a systematic and a narrative review. The outcome of interest was the bacteriological cure (BC). Results: The findings revealed that antibiotic treatment resulted in improved BC rates for cases caused by Streptococci. For cases caused by Escherichia (E.) coli, antibiotic therapy showed no significant improvement in BC rates compared to non-antibiotic treatment, suggesting that antibiotics may be often unnecessary for these cases due to self-limiting tendencies. However, severe E. coli mastitis warrants systemic antibiotic treatment due to potentially life-threatening complications. Klebsiella spp. mastitis showed better cure rates with antibiotic therapy. Conclusions: This study underscores the importance of regular pathogen diagnostics to guide appropriate treatment, advocating for the use of on-farm rapid tests to reduce unnecessary antibiotic use while ensuring effective treatment outcomes. Full article

Mastitis is a major issue in dairy cows, with subclinical mastitis (SCM) being hard to detect and potentially progressing to clinical mastitis. Antibiotic use raises concerns about resistance and milk contamination, highlighting the need for natural alternatives. Sodium alginate (SA), known for its antioxidant and immunomodulatory properties, may offer a solution, though its effects on mastitis are unclear. Intramammary infusion of 1% SA (30 mL) was tested in both healthy cows (n = 8; somatic cell count, SCC ≤ 100,000 cells/mL) and those with SCM (n = 12; SCC ≥ 200,000 cells/mL). The results showed that SA significantly increased SCC in both healthy and SCM cows, with peak levels at 48 h, returning to baseline levels thereafter. In cows with SCM, SA treatment led to a 58.3% cytological and 54.5% bacteriological cure rate after 14 days. Additionally, significant downregulation was observed in tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-4, IL-6, and interferon (IFN)-γ. Conversely, the levels of IL-8, IL-10, and IL-12 initially increased, then declined gradually. Importantly, there were no significant effects on milk composition. These findings suggest that SA may offer an alternative to antibiotics, aiding in immune response and bacterial clearance without the risk of antibiotic residues, thus preventing SCM progression to clinical mastitis. Full article

A Lactococcus (L.) lactis strain producing antimicrobial and anti-inflammatory biomolecules (mainly 1,4-Diaza-2,5-dioxobicyclo[4.3.0]nonanes and pyrazine-derivatives) was tested for its capacity to cure clinical endometritis in buffaloes compared to conventional antibiotic-based treatment. Clinical endometritis-diagnosed buffaloes (n = 16/group) were infused intrauterine with four doses of 10⁹ CFU-free (FLC group) or nanoencapsulated L. lactis (NLC group) and compared to those that received three doses of saline + a single dose of 500 mg cephapirin benzathin (AB group) or four doses of saline (control, C group) every other day. Endometrium samples were analyzed for cytological (polymorphonuclear cells, PMN), bacteriological, and proinflammatory mRNA expression. Uterine wash and blood samples were collected to determine proinflammatory cytokine concentrations and metabolites in the blood samples. The reproductive performance of buffaloes was assessed. Compared to the C group, the AB and NLC groups had the lowest percentage of PMN, followed by those in the FLC group (p < 0.05). All treated buffaloes had significantly lower numbers of pathogens than the control buffaloes. Compared to control, all treatments significantly down-regulated endometrial proinflammatory encoding mRNA expression. The concentrations of IL1B, TNFAIP7, and leukocyte esterase activity in the uterine washings were significantly decreased in the AB and NLC groups compared to the C and FLC groups. All treatments significantly decreased concentrations of serum proinflammatory cytokines compared to control. Both the AB and NLC groups had significantly lower concentrations of serum NEFA than the C and FLC groups. The percentage of control buffaloes having an echogenic uterus and PVD score > 2 was significantly higher than those in the treated buffaloes with higher numbers of corpora lutea, higher conception rates, and shorter days open than control buffaloes (p < 0.05). In conclusion, L. lactis-producing antimicrobial and anti-inflammatory metabolites reduce uterine inflammatory responses and improve fertility in buffaloes. Full article

Oritavancin (ORI) is a semisynthetic lipoglycopeptide approved as a single 1200 mg dose intravenous infusion for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by Gram-positive organisms in adults. The pharmacokinetic/pharmacodynamic (PK/PD) linear kinetic profile and long terminal half-life (~393 h) of ORI make it therapeutically attractive for the treatment of other Gram-positive infections for which prolonged therapy is needed. Multidose regimens are adopted in real-world clinical practice with promising results, but aggregated efficacy data are still lacking. A comprehensive search on PubMed/Medline, Scopus, Cochrane and Google Scholar databases was performed to include papers published up to the end of January 2023. All articles on ORI multiple doses usage, including case reports, with quantitative data and relevant clinical information were included. Two reviewers independently assessed papers against the inclusion/exclusion criteria and for methodological quality. Differences in opinion were adjudicated by a third party. From 1751 potentially relevant papers identified by this search, a total of 16 studies met the inclusion criteria and were processed further in the final data analysis. We extracted data concerning clinical response, bacteriologic response, mortality and adverse events (AEs). From the 16 included papers, 301 cases of treatment with multidose ORIs were identified. Multidose regimens comprised an initial ORI dose of 1200 mg followed by 1200 mg or 800 mg subsequent doses with a varying total number and frequency of reinfusions. The most often treated infections and isolates were osteomyelitis (148; 54.4%), ABSSSI (35; 12.9%) and cellulitis (14; 5.1%); and MRSA (121), MSSA (66), CoNS (17), E. faecalis (13) and E. faecium (12), respectively. Clinical cure and improvement by multidose ORI regimens were observed in 85% (231/272) and 8% (22/272) patients, respectively. Multidose ORI was safe and well tolerated; the most frequent AEs were infusion-related reactions and hypoglycemia. A multidose ORI regimen may be beneficial in treating other Gram-positive infections besides ABSSSIs, with a good safety profile. Further studies are warranted to ascertain the superiority of one multidose ORI scheme or posology over the other. Full article

Infectious mastitis is the most prevalent health problem in dairy cattle that can result in permanent economic losses on dairy farms. The micronised purified flavonoid fraction (MPFF) is a biocompatible active polyphenolic compound derived from flavonoid glycosides which exhibits several antimicrobial, anti-inflammatory, and phlebotonic properties. The goal was to assess the effects of an alternative therapy for mastitis based on MPFF intramammary infusions in late lactation in dairy cows naturally infected by Staphylococcus spp. The California Mastitis Test (CMT scores) was performed to detect mastitis-positive quarters in twelve dairy farms. All cows were screened for immune response by measuring somatic cell counts (SCCs; cells/mL) in milk samples from each quarter. In addition, bacteriological identification, pathogenic bacterial isolates, and total bacterial counts (TBCs; CFU/mL) were assessed before (day 0, last milking day) and after (day 3 post-calving) MPFF application. Antimicrobial sensitivity patterns of the pathogenic isolated bacteria were evaluated. Finally, cure rates (%) were determined for each MPFF treatment. Around 15 mastitis-related genera were isolated. Staphylococcus aureus (25.2%) and coagulase-negative Staphylococci (CNS; 22.4%) were the most prevalent pathogens. No statistical differences were observed in SCCs and TBCs after low, medium, and high MPFF dose administration in S. aureus-positive mastitis cases (p > 0.05). However, differences were observed in SCCs and TBCs after medium and high MPFF dose administration in CNS-positive quarters (p < 0.05). The pathogenic bacteria isolate reduction after MPFF applications showed a dose-response fashion (p < 0.01) while isolates obtained from controls and low MPFF-treated quarters remained similar, irrespective of the pathogen (p > 0.05). Sensitivity patterns were variable, although S. aureus remained resistant, irrespective of the MPFF dose. However, CNS showed a dose-response sensitivity pattern. Finally, the cure rate (%) on day 3 post-partum improved significantly using medium and higher MPFF doses in CNS-positive quarters (p < 0.05). In conclusion, MPFF treatment was found to be more effective for CNS-positive cases in the late lactation due to noticeable dose-specific responses regarding somatic cells, bacterial counts, sensitivity patterns, and cure rates in dairy cattle. Full article

Antimicrobials are widely used to cure intramammary infections (IMI) in dairy cows during the dry period (DP). Nevertheless, the IMI cure is influenced by many factors and not all quarters benefit from antimicrobial dry cow treatment (DCT). To evaluate the true effect of antibiotic DCT compared to self-cure and the role of causative pathogens on the IMI cure, a retrospective cross-sectional study was performed. The analysis included 2987 quarters infected at dry-off (DO). Information on DCT, causative pathogens, somatic cell count, milk yield, amount of lactation, Body Condition Score, and season and year of DO were combined into categorical variables. A generalized linear mixed model with a random cow, farm and year effect and the binary outcome of bacteriological cure of IMI during the DP was conducted. In the final model, a significant effect (p < 0.05) on DP cure was seen for the DO season and the category of causative pathogens (categories being: Staphylococcus aureus, non-aureus staphylococci, streptococci, coliforms, ‘other Gram-negative bacteria’, ‘other Gram positive bacteria’, non-bacterial infections and mixed infections), while antibiotic DCT (vs. non-antibiotic DCT) only showed a significant effect in combination with the pathogen categories streptococci and ‘other Gram-positive bacteria’. Full article

Increasing pressure on animal and human health as well as food security, due to antimicrobial resistance, is leading to increased demand for natural-product-derived antibiotics worldwide. Considering the importance of bovine mastitis as well as the huge challenge posed by mastitis therapy in cattle production, the main goal of this research was to evaluate the effectiveness of the essential oil-based pharmaceutical (Phyto-Bomat), as an alternative to the existing treatment with antibiotics. The therapeutic response of the cows was monitored using clinical and bacteriological cure of the proposed formulation. Among 550 dairy cows, 75 were diagnosed with a clinical or subclinical form of mastitis and divided into three experimental groups: treated with antibiotic; Phyto-Bomat; antibiotic and Phyto-Bomat. Indicators of bacteriological cure were somatic cell count (SCC), total bacterial count, and causative agent isolation, while the clinical cure was accessed by observing physical udder conditions. All mentioned indicators were assessed before and after the treatment (1st and 7th day post-treatment), with all of the three therapeutic protocols. After Phyto-Bomat treatment, no visible signs of irritation were noticed, while no significant effect in reducing SCC and total bacterial count was observed. Phyto-Bomat has shown promising results in the treatment of mastitis, without the risk of udder irritation, alone or in combination with antibiotics as part of a mastitis control program during lactation. Full article

Lactococcus garvieae (L. garvieae) is a pathogenic gram-positive, catalase-negative (GPCN) bacterium that causes bovine mastitis. A total of 49 L. garvieae isolates were identified from 1441 clinical mastitis (CM) samples. The pathogenic effects of L. garvieae were studied with two infection models: bovine mammary epithelial cells cultured in vitro and murine mammary infections in vivo. The overall farm prevalence was 15.5% (13/84 farms in 9/19 provinces) and sample prevalence was 3.40% (49/1441). Post-treatment somatic cell count (SCC) post L. garvieae infection was significantly higher than the other GPCN pathogens isolated, and the bacteriological cure fraction was 41.94% (13/31) after intramammary antibiotic treatment. All L. garvieae isolates were resistant to rifaximin, 12.24% of isolates were resistant to cephalexin, and 10.20% (5/49) were multidrug-resistant (MDR). The most prevalent virulence genes were Hemolysin 1 (hly1)(100%), Hemolysin 2 (hly2) (97.96%), NADH oxidase (NADHO) (100%), Superoxide dismutase (SOD) (100%), Adhesin Pav (Pav) (100%), Adhesin PsaA (PsaA) (100%), Enolase (eno) (100%), Adhesin cluster 1(AC1) (100%), Adhesin cluster 2 (AC2) (100%), and several exopolysaccharides. L. garvieae rapidly adhered to bovine mammary epithelial cells, resulting in an elevated lactate dehydrogenase release. Edema and congestion were observed in challenged murine mammary glands and bacteria were consistently isolated at 12, 24, 48, 72, and 120 h after infection. We concluded that L. garvieae had good adaptive ability in the bovine and murine mammary cells and tissue. Given the resistance profile, penicillin and ampicillin are potential treatments for CM cases caused by L. garvieae. Full article