Search Results (622)

Background: High infectious disease burden and uncontrolled antibiotic usage across human, animal, and environmental contaminants make antimicrobial resistance (AMR) a growing public health problem in Africa. Mobile genetic elements (MGEs) such plasmids, transposons, integrons, conjugative elements, and phages help spread AMR via horizontal gene transfer (HGT) across human, animal, food, and environmental sources. Despite growing evidence for antibiotic resistance genes (ARGs), Africa lacks a one-health-focused synthesis of mobile genetic element-mediated AMR. Objective: This systematic review and meta-analysis aimed to consolidate information on MGEs and ARGs in AMR dissemination throughout Africa’s one health interface. Methods: The literature was searched using PubMed, Scopus, and ScienceDirect. Observational. molecular epidemiology, whole genome sequencing (WGS), and metagenomic investigations of MGE-associated AMR in Africa were eligible. The study selection, data extraction, and quality assessment were performed by two independent reviewer and quality was graded using ROBVIS 2 utilizing Rayyan software. Narrative synthesis, random-effect meta-analysis, subgroup analysis, and meta-regression were utilized. Results: A total of 109 studies were included, with 91 studies contributing to the meta-analysis. MGEs reported were plasmids (71.7%) and integrons (54.8%). ARGs carried by MGEs were blaCTMX-M-15 (78.6%), Sul2 (69.6%), blaTEM (59.1%), and tetA (49.9%). Horizontal gene transfer was seen in 259 instances; however, transmission was unclear. In 442 observations, transmission pathways across human, animal, and environmental interfaces showed AMR prevalence of 75.1% in human, 98.0% in human–animal, and 61.3% in one health interface. Whole-genome sequencing was the most frequently used method for detecting MGEsThe pooled pathogen and AMR prevalence rates were 73.3% (95% CI: 60.5–83.7%) and 94% (95% CI: 85–98%), with significant heterogeneity (I² = 97.8% and 97.4%, respectively). The prevalence of Escherichia coli was 93% and Salmonella enterica 85% in subgroup analysis. Fluoroquinolones, aminoglycosides, and beta-lactams were prevalent in humans (89.7%) and human–animal interactions (98.0%) according to AMR Class. Conclusions: Horizontal gene transfer has propagated MGE-mediated antimicrobial resistance across human, animal, and environmental interfaces in Africa. To combat AMR in Africa, coordinated, genomics-informed One Health surveillance and antibiotic stewardship are needed. Due to variability and publication bias, these data should be considered cautiously. Pooled data may only show descriptive patterns, and not necessarily precise continent-wide prevalence estimates. Full article

Objective: Given the increasing use of outpatient parenteral antimicrobial therapy (OPAT) and the clinical challenges posed by Pseudomonas aeruginosa infections, this study aimed to evaluate the effectiveness and safety of OPAT for the treatment of P. aeruginosa infections in a real-world cohort. Methods: We conducted a prospective observational study with retrospective analysis including adult patients with P. aeruginosa infections treated within a multidisciplinary OPAT program shared by two tertiary hospitals between November 2012 and December 2024. Clinical characteristics, infection type, antimicrobial therapy, resistance patterns, source control, and clinical outcomes were recorded. Primary outcomes were treatment failure during OPAT and within 30 days after OPAT completion. Secondary outcomes included adverse events and vascular access complications. Bivariate and multivariable logistic regression analyses were performed to identify factors associated with treatment failure. Results: A total of 290 patients were included. The most frequent infections were bronchiectasis exacerbations (39.7%) and complicated urinary tract infections (15.2%). Most patients received monotherapy (72.8%), mainly ceftazidime, while 27.2% received combination therapy with a beta-lactam plus an aminoglycoside. Treatment failure occurred in 7.6% of patients during OPAT and in 15.5% within 30 days after OPAT completion, with an overall clinical success rate of 77%. Male sex and chronic obstructive pulmonary disease (COPD) were independently associated with failure during OPAT. At 30 days, higher Charlson comorbidity index, COPD exacerbation, and endovascular infection were associated with failure, whereas combination therapy was associated with a lower risk of failure. Antimicrobial-related adverse events were rare (3.2%). Conclusions: Our results support OPAT as an effective and safe strategy for managing P. aeruginosa infections in clinically stable patients. Patients with COPD, either as a comorbidity or during an exacerbation, and those with a higher Charlson score may require closer follow-up. Full article

Background/Objectives: Integrons are genetic platforms that allow bacteria to acquire antimicrobial resistance (AMR) genes, making them a focal point for many AMR studies and surveillance programs. This study investigated how the prevalence of integrons (intI and attI genes) in third-generation cephalosporin-resistant E. coli (3GCR-Ec) varied across three different sources (i.e., healthy children, domestic animals and urinary tract infections). The study aimed to determine how different classes of AMR genes vary among 3GCR-Ec with integrons present versus those where integrons are absent. Methods: We analyzed 3GCR-Ec isolates collected from semirural parishes of Eastern Quito, Ecuador, that included: (1) 3GCR-Ec from healthy children (n = 946), (2) 3GCR-Ec from domestic animal species (n = 673), and 3GCR-Ec from patients with urinary tract infections (UTIs) (n = 138). Genomic analyses were performed for all 1757 sequences to determine how the presence and absence of integrons was associated with AMR gene carriage. Results: Among the total sequences of 3GCR-Ec evaluated across all datasets, nearly one-third (31%) were integron-negative. 3GCR-Ec from UTI patients, however, had a higher percentage containing integrons (79%). Across all sets of 3GCR-EC, integron-positive isolates carried an average of 10.3 (±3.0 SD) AMR genes versus 4.8 (±2.5 SD) AMR genes in integron-negative isolates. This study found that between 21% to 33% of 3GCR-Ec across the three different sources lacked integrons but maintained the ability to carry diverse classes of AMR genes, including beta-lactams, aminoglycosides, tetracyclines, and multidrug resistance mechanisms (e.g., general-purpose efflux pumps). Conclusions: While integrons were associated with greater AMR genes on average, the study highlights that solely relying on integrons for tracking drug-resistant bacteria misses a substantive portion of AMR that is present in integron-negative strains. Full article

Background: Kounis syndrome is an allergic acute coronary syndrome precipitated by coronary vasospasm, plaque destabilization, stent thrombosis, or bypass occlusion. Cardiac surgery represents a uniquely high-risk setting due to cardiopulmonary bypass–associated inflammation and exposure to multiple pharmaceutical agents. Importantly, Kounis syndrome remains underrecognized in this context, as classical signs of anaphylaxis may be masked under general anesthesia and cardiopulmonary bypass, while ischemic manifestations may be misattributed to other perioperative conditions. Methods: A narrative review of PubMed-indexed literature was conducted to synthesize current evidence on the pathophysiology, perioperative triggers, clinical presentation, diagnostic strategies, and management of Kounis syndrome in cardiac surgery, with emphasis on intraoperative recognition and surgical decision-making. Published cases were retrieved involving perioperative cardiac surgery patients with a definite diagnosis of Kounis syndrome. Additionally, cases presenting with severe perioperative anaphylaxis and life-threatening cardiovascular involvement (grade III with cardiovascular collapse and grade IV with cardiac arrest) were included as possible Kounis syndrome, reflecting real-world diagnostic uncertainty in the intraoperative setting. Results: The literature review identified five cases of definite Kounis syndrome and ten cases of possible Kounis syndrome, including three cases with cardiovascular collapse and seven cases with cardiac arrest. Recurrent episodes were reported in several patients, particularly due to re-exposure to the triggering agent. In the context of cardiac surgery, Kounis syndrome is most frequently triggered by chlorhexidine, protamine, antibiotic prophylaxis, and anesthetic agents. The clinical presentation is often subtle during cardiopulmonary bypass. Vasoplegia, pulmonary hypertension, ventricular dysfunction, new regional wall-motion abnormalities, and hyperdynamic ventricles on transesophageal echocardiography commonly precede overt electrocardiographic changes. Diagnosis is primarily clinical and relies on intraoperative ultrasound, hemodynamic monitoring, serum tryptase, serum troponin, and, when indicated, coronary angiography. A dual-pathway approach addressing both anaphylaxis and myocardial ischemia is essential; however, one component may predominate, particularly in perioperative patients with limited clinical information, potentially leading to misdiagnosis. A multidisciplinary approach is therefore required for rapid diagnosis and individualized management. In refractory cases, cardiopulmonary bypass or ventricular assist devices may provide lifesaving support. Conclusions: Kounis syndrome remains underrecognized in cardiac surgery but carries significant morbidity. Increased clinical awareness, multidisciplinary collaboration, structured diagnostic approaches, and preventive strategies are essential to improve outcomes and reduce the risk of recurrence during future procedures. Full article

Background and Objectives: Systemic mastocytosis (SM) is a clonal mast cell disorder characterized by abnormal mast cell accumulation and activation in multiple organs, leading to mediator-related symptoms, including anaphylaxis. Drug hypersensitivity reactions (DHRs) are a major clinical challenge in SM, but their frequency and characteristics remain undefined. This study aimed to evaluate the frequency of drug allergy, identify high-risk drug groups, investigate reaction characteristics, and examine the relationship between drug reactions, baseline serum tryptase levels, and SM subtypes in patients with SM. Materials and Methods: We retrospectively analyzed 34 patients diagnosed with SM between 2009 and 2024 at Ege University Faculty of Medicine. Clinical features, SM subtypes, baseline serum tryptase levels, and DHR characteristics were recorded. Reactions to antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, anesthetics, radiocontrast media (RCM), and COVID-19 vaccines were graded using the Ring and Messmer anaphylaxis classification. Results: Among 34 patients, the mean age was 48.6 ± 13.3 years, 53% were male, and 10 (29.4%) had DHRs. The most common culprit drugs were NSAIDs (17.6%) and β-lactam antibiotics (14.7%). Anaphylaxis was the predominant reaction, frequently associated with hypotension. In 5 patients (14.7%), drug-induced anaphylaxis was the initial and only manifestation of SM. No hypersensitivity reactions occurred to quinolones, general anesthetics, or COVID-19 vaccines. Median baseline tryptase was 50.25 µg/L (min–max: 8.59–200.00) overall, and 41.85 µg/L (min–max: 19.00–200.00) among those with DHRs. Conclusions: Patients with SM are at increased risk of severe DHRs, particularly to NSAIDs and beta-lactam antibiotics. In some patients, drug allergy may be the first and only manifestation of SM. Measurement of baseline serum tryptase is essential in patients with drug-induced anaphylaxis. A comprehensive allergy assessment, including tolerance testing and individualized counseling, is crucial to ensure safe pharmacological management. Full article

Several species of the genus Acinetobacter are nosocomial pathogens with a well-documented ability to acquire resistance to multiple antibiotics. Although Acinetobacter is one of the most abundant genera in meat processing environments, data on this genus outside of clinical environments remains limited. The objective of this study was to ascertain the prevalence, diversity and antimicrobial resistance profile of Acinetobacter spp. in 200 samples collected from food contact surfaces, non-food contact surfaces, carcasses and final meat cuts across five pork, chicken and beef processing facilities, each comprising physically connected slaughterhouses and meat processing plants. Acinetobacter spp. were detected in 80% (95% CI = 71–87%) and 70% (95% CI = 60–79%) of samples from slaughterhouses and processing plants, respectively. The facilities harboured a wide diversity of Acinetobacter species, with 27 different species identified. Acinetobacter baumannii was the species most frequently detected. Whole-genome sequencing of 18 Acinetobacter spp. isolates revealed the presence of ARGs conferring resistance to beta-lactams, tetracyclines and aminoglycosides, and disclosed phylogenetic relationships with isolates from fresh meat. Phenotypic resistance to beta-lactams, fluoroquinolones, aminoglycosides, folate pathway inhibitors and/or tetracyclines was observed in 77.8% of the sequenced isolates, with 44.4% classified as multidrug-resistant. These findings identify meat processing environments as an important reservoir of Acinetobacter spp. and highlight the need for further investigation to prevent the dissemination of antimicrobial-resistant strains. Full article

Arcanobacterium haemolyticum is a facultative anaerobic, Gram-positive bacillus that has garnered attention due to its role in human infections, particularly among adolescents and young adults. Traditionally associated with pharyngitis, this organism is increasingly recognized for its involvement in systemic infections, including bacteremia, central nervous system abscesses, and Lemierre’s syndrome. The pathogenicity of A. haemolyticum is attributed to its production of hemolysins and neuraminidase, facilitating tissue invasion and immune evasion. Clinically, infections often present with sore throat, fever, and a characteristic scarlatiniform rash, which can lead to their misdiagnosis as streptococcal pharyngitis. Severe manifestations, though rare, have been documented, particularly in immunocompromised individuals. Diagnosis is challenging due to the organism’s slow growth and potential misidentification as diphtheroids in cultures. Accurate identification necessitates specific culture conditions and biochemical testing. Treatment typically involves beta-lactam antibiotics; however, the emergence of resistance patterns necessitate susceptibility testing to guide therapy. This review aims to consolidate current knowledge on A. haemolyticum, emphasizing its clinical presentations, diagnostic challenges, and management strategies, thereby enhancing recognition and treatment of infections caused by this emerging pathogen. Full article

Rates of foodborne infectious disease are increasing globally. The One Health zoonoses report shows increasing cases of shigatoxigenic Escherichia coli, campylobacteriosis, salmonellosis and listeriosis in the last 5 years. The ESKAPE pathogens are the top priority due to their alarming rate of resistance to broad-spectrum beta-lactams, carbapenems, glycopeptides, fluoroquinolones, aminoglycosides and biocide solutions. Research assessing alternative biocontrol options highlight the advantages of bacteriophages in the control of resistant bacterial species. Phage formulations including ListShield^TM and SalmoFresh^TM have gained FDA approval for food production. As biocontrol agents, however, phages are limited by their specificity in a multispecies environment, the presence of environmental variables and bacterial resistance mechanisms. Genetic modification and the use of phage cocktails aim to overcome such limitations. Future research is warranted in a harmonised approach supported by a defined legal framework to establish best formulation and exposure protocols. This review discusses phages as biocontrol agents in the control of high-risk pathobionts associated with foodborne illness. Pathobionts associated with bovine livestock are discussed due to the morbidity and incidence of disease associated with such pathogens. Full article

Background: The goal of this study was to characterize the microbial etiology, antimicrobial susceptibility, and temporal resistance trends of early-onset neonatal sepsis (EOS) pathogens in a tertiary neonatal intensive care unit over 10 years (2014–2023), assessing empirical therapy adequacy and mortality associations. Methods: Retrospective analysis was performed on the positive blood cultures of neonates with confirmed EOS, born between 1 January 2014 and 31 December 2023. Blood was aseptically collected into PEDS Plus/BC bottles, incubated using the BACTEC system, with pathogen identification by biochemical assays or MALDI-TOF MS. Susceptibility testing followed EUCAST disk-diffusion standards, with additional resistance assays. Results: Among 6631 NICU admissions, 39 neonates met EOS criteria (31 preterm, 8 term). In preterm infants, Gram-negative Enterobacterales—mainly E. coli (n = 20)—predominated, while GBS was most common in term infants. All GBS isolates (n = 7) were susceptible to benzylpenicillin and vancomycin. Although 90% of E. coli were ampicillin-resistant, 90–95% remained susceptible to third-generation cephalosporins, piperacillin–tazobactam, and aminoglycosides. Two E. coli isolates produced ESBL but remained susceptible to aminoglycosides and carbapenems. Mortality was higher in E. coli EOS (50%) than in GBS (0%) or other pathogens (25%), with borderline significance (p = 0.0547; adjusted RR 1.55, 95% CI 0.54–4.41). Ampicillin resistance was not associated with increased mortality. No annual resistance trends were observed. Conclusions: In this 10-year NICU cohort, the etiology of EOS differed markedly between preterm and term neonates. Recommended empirical ampicillin–aminoglycoside therapy demonstrated in vitro efficacy against most neonatal bloodstream isolates pending pathogen identification. However, the widespread ampicillin resistance, particularly among E. coli strains, supports consideration of cephalosporin–aminoglycoside combinations or meropenem monotherapy when rapid beta-lactam bactericidal activity is clinically essential. Mortality was higher in E. coli EOS, though not statistically significant, and unrelated to ampicillin resistance. Full article

Background: Localized susceptibility data supports development of a pediatric-specific antibiogram to guide empiric therapy for ear infections within the British Columbia community setting. The aim of the current student was to construct an antibiogram from community-collected ear culture isolates to support antibiotic selection for ear infections in communities. Methods: Data were collected from patients <18 years of age with specimens submitted to LifeLabs British Columbia between 2020 and 2024, which included 2338 ear specimens. Organisms with ≥30 isolates undergoing antimicrobial susceptibility testing were included for analysis. Results: The most frequently identified organisms included methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA, n = 648 and 80, respectively), Group A Streptococcus (GAS, n = 357), Pseudomonas aeruginosa (n = 316), Streptococcus pneumoniae (n = 105), and Haemophilus influenzae (n = 75). Beta-lactam antibiotics maintained high activity (>90%) against MSSA, GAS, and S. pneumoniae, while clindamycin and erythromycin showed significantly lower sensitivity against both MSSA (84% and 82%, respectively) and MRSA (79% and 50%, respectively) (p < 0.001). Trimethoprim–sulfamethoxazole and tetracycline demonstrated 99% and 97% susceptibility for MSSA, respectively, and 94% and 85% for MRSA, respectively. Conclusions: Beta-lactam antibiotics remain suitable for treatment against the pathogens S. pneumoniae, GAS, and MSSA, while trimethoprim–sulfamethoxazole is more suitable for MRSA. Full article

Background: Staphylococci, recognized for their virulence and antibiotic resistance, are important in both human and veterinary medicine. Loss of sensitivity to beta-lactam antibiotics, such as ampicillin, complicates therapy, prompting the search for alternative antibacterials or ways to increase drug efficacy. Silver and gold nanoparticles (AgNPs, AuNPs) are promising on their own or in combination with antibiotics. Methods: The aim of this study is to compare the biological activity of pure, washed AgNPs and AuNPs with biosynthesized nanoparticles from Alchemilla vulgaris (AgNPs-Av and AuNPs-Av). Their antibacterial, antibiofilm, and biofilm-eradication effects on the tested antibiotic-resistant, biofilm-forming staphylococci (Methicillin-resistant Staphylococcus aureus (MRSA) and multiresistant Non-aureus staphylococci and mammaliicocci (NASM)) were evaluated using in vitro microdilution methods. Results: AgNPs-Av and AuNPs-Av inhibited bacterial growth at 50 μg/mL, while a significant suppression of biofilm formation was observed at just 25 μg/mL. Our research showed that neither AuNPs-Av nor AuNPs disrupts bacterial biofilm. AgNPs-Av effectively eradicated the biofilm at 50 μg/mL. NPs and ampicillin at subinhibitory antibiotic concentrations against the tested staphylococci. The results showed significant antibacterial and antibiofilm effects (p = 0.001). Partially, biofilm-eradication activity and strong antibiotic potentiation were also detected. Conclusions: These findings highlight the importance of rational combination therapy to improve antibiotic effectiveness and reduce bacterial resistance. Full article

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) has been added to the World Health Organization’s list as a high-priority pathogen for which new antibiotics are urgently needed. Herein, we investigated the association between resistance/virulence genes and high-risk CRPA clinical isolates by whole genome sequencing (WGS). Methods: Between 2019 and 2025, twenty-six CRPA strains from patients hospitalized in the “Renato Dulbecco” University Hospital were characterized. WGS analysis was performed using the next generation sequencing (NGS) technique. Multi-locus sequence typing (MLST) prediction was performed. Antibiotic resistance genes were detected using Antibiotic Resistance Gene-ANNOTation, Comprehensive Antibiotic Resistance Database, and ResFinder. Virulence genes were identified by the Virulence Factor Database. Results: The MLST analysis detected 14 different sequence types (ST). The 26 strains exhibited the same resistome profile: aac(3)-Ic, aphA15, catB7, catB10, cmlA, blaCARB, blaVIM-1, and tetG genes. The genes encoding enzymes involved in resistance to chloramphenicol and beta-lactams were found in all isolates using the three databases. Biofilm formation genes, metalloproteinase, chemotaxis, fimbriae, and pyoverdine were identified in all strains. Genes of the type III secretion system exoS, exoT, exoU, and exoY were found in 46.15%, 84.61%, 53.84%, and 84.61% of the strains, respectively. Conclusions: The analysis of the 26 clinical isolates showed high clonal heterogeneity, with a predominance of ST235, a high-risk clone associated with multiple resistances. Interestingly, cefiderocol resistance was carried by 4/8 isolates belonging to the ST235 strain. The surveillance based on resistome and virulome analysis could monitor the dynamic evolution of high priorityhigh-priority pathogens to guide clinical treatment and to adapt healthcare control measures, limiting their spread in the near future. Full article

Antimicrobial resistance (AMR) poses a critical challenge to global health, with food animal production systems recognized as significant reservoirs of antimicrobial-resistant bacteria. This study evaluated the prevalence and distribution of antimicrobial resistance genes (ARGs) and virulence factors (VFs) across small-scale poultry and cattle farms. A total of 468 samples (soil, feces, water, and natural land soil) were collected from four farms and analyzed using shotgun metagenomics. Proteobacteria (34.91%) were the dominant phylum across environments, followed by Cyanobacteria (15.67%), Actinobacteria (14.95%), Firmicutes (10.57%), and Bacteroidetes (8.69%). Tetracycline (33.41%) and beta-lactam (30.30%) resistance genes were the most abundant, with macrolide (9.32%) and aminoglycoside (8.39%) resistance also detected. Both tetracycline and beta-lactam resistance genes were significantly enriched across sample types (p < 0.05). The detection of diverse VFs alongside ARGs highlights the pathogenic potential of bacterial communities in these production systems. Collectively, the findings reveal that small-scale animal farms are reservoirs of AMR with implications for public health through foodborne transmission. Targeted surveillance and control measures are necessary to prevent the dissemination of ARGs into the broader food chain and to safeguard both human and animal health. Full article

Penicillin (PCN) allergies are frequently reported despite a true prevalence of less than 1%, leading to unnecessary avoidance of beta-lactams, broader antimicrobial use, and increased healthcare costs. Pharmacist-driven de-labeling programs offer a strategy to improve antimicrobial stewardship. This single-center, retrospective study evaluated hospitalized adults with a documented PCN allergy and screened by the pharmacist-driven penicillin allergy de-labeling service (PADLS) between 16 January and 26 June 2025. Patients were categorized into a screened cohort and a Full Allergy Reconciliation (FAR) cohort if interviewed using PEN-FAST. Eligible patients underwent direct oral challenge (DOC), penicillin skin testing (PST) plus DOC, or direct de-labeling based on PEN-FAST scoring. Sixty-three patients were screened, and 32 (50.8%) underwent full reconciliation. Among FAR patients, the median PEN-FAST score was 0, and 25 (78.1%) underwent DOC. De-labeling was successful in 28 FAR patients (87.5%). One patient (4%) experienced a mild reaction. Allergy field updates occurred in 69.8% of screened and 96.9% of FAR patients. Antibiotic optimization occurred in 12 FAR patients, saving 78 days of therapy. Estimated cost savings totaled $37,632. PADLS effectively and safely de-labeled PCN allergies, resulting in improved antimicrobial selection, and could generate cost savings, supporting broader implementation of pharmacist-led allergy stewardship programs. Full article

Background: Bovine mastitis is a leading cause of economic loss in dairy farming and is increasingly complicated by antimicrobial resistance (AMR), posing challenges to treatment and public health. Objectives: This study aimed to investigate the prevalence, bacterial etiology, and AMR patterns of mastitis pathogens in dairy herds from the Banat region of Romania. Materials and Methods: A retrospective analysis was conducted on 420 dairy cows from five localities. Mastitis diagnosis involved clinical examination, indirect tests (California Mastitis Test (CMT), R-Mastitest), and bacteriological culture. Antimicrobial susceptibility was assessed using the VITEK^® 2 system. Results: Out of 420 cows, 120 (28.6%) were diagnosed with mastitis. The predominant pathogens were Staphylococcus aureus (33.3%) and Streptococcus agalactiae (22.5%). Most infections were monomicrobial (70%) and affected a single under quarter (77.5%). Beta-lactam resistance was widespread among both Gram-positive and Gram-negative isolates, particularly against penicillin and ampicillin. Multidrug-resistant (MDR) strains were identified in 33.3% of all isolates, with 100% of Gram-negative isolates exhibiting MDR profiles. Conclusions: The high prevalence of S. aureus and S. agalactiae, along with widespread beta-lactam resistance and frequent MDR phenotypes, highlights the urgent need for routine AMR surveillance and targeted antimicrobial therapy in bovine mastitis control programs. Full article