The use of aminoglycosides in animals within the EU: development of resistance in animals and possible impact on human and animal health: a review.

Aminoglycosides (AGs) are important antibacterial agents for the treatment of various infections in humans and animals. Following extensive use of AGs in humans, food-producing animals and companion animals, acquired resistance among human and animal pathogens and commensal bacteria has emerged. Acquired resistance occurs through several mechanisms, but enzymatic inactivation of AGs is the most common one. Resistance genes are often located on mobile genetic elements, facilitating their spread between different bacterial species and between animals and humans. AG resistance has been found in many different bacterial species, including those with zoonotic potential such as Salmonella spp., Campylobacter spp. and livestock-associated MRSA. The highest risk is anticipated from transfer of resistant enterococci or coliforms (Escherichia coli) since infections with these pathogens in humans would potentially be treated with AGs. There is evidence that the use of AGs in human and veterinary medicine is associated with the increased prevalence of resistance. The same resistance genes have been found in isolates from humans and animals. Evaluation of risk factors indicates that the probability of transmission of AG resistance from animals to humans through transfer of zoonotic or commensal foodborne bacteria and/or their mobile genetic elements can be regarded as high, although there are no quantitative data on the actual contribution of animals to AG resistance in human pathogens. Responsible use of AGs is of great importance in order to safeguard their clinical efficacy for human and veterinary medicine.

Public health risk of antimicrobial resistance transfer from companion animals.

Antimicrobials are important tools for the therapy of infectious bacterial diseases in companion animals. Loss of efficacy of antimicrobial substances can seriously compromise animal health and welfare. A need for the development of new antimicrobials for the therapy of multiresistant infections, particularly those caused by Gram-negative bacteria, has been acknowledged in human medicine and a future corresponding need in veterinary medicine is expected. A unique aspect related to antimicrobial resistance and risk of resistance transfer in companion animals is their close contact with humans. This creates opportunities for interspecies transmission of resistant bacteria. Yet, the current knowledge of this field is limited and no risk assessment is performed when approving new veterinary antimicrobials. The objective of this review is to summarize the current knowledge on the use and indications for antimicrobials in companion animals, drug-resistant bacteria of concern among companion animals, risk factors for colonization of companion animals with resistant bacteria and transmission of antimicrobial resistance (bacteria and/or resistance determinants) between animals and humans. The major antimicrobial resistance microbiological hazards originating from companion animals that directly or indirectly may cause adverse health effects in humans are MRSA, methicillin-resistant Staphylococcus pseudintermedius, VRE, ESBL- or carbapenemase-producing Enterobacteriaceae and Gram-negative bacteria. In the face of the previously recognized microbiological hazards, a risk assessment tool could be applied in applications for marketing authorization for medicinal products for companion animals. This would allow the approval of new veterinary medicinal antimicrobials for which risk levels are estimated as acceptable for public health.

Pleuromutilins: use in food-producing animals in the European Union, development of resistance and impact on human and animal health.

Pleuromutilins (tiamulin and valnemulin) are antimicrobial agents that are used mainly in veterinary medicine, especially for swine and to a lesser extent for poultry and rabbits. In pigs, tiamulin and valnemulin are used to treat swine dysentery, spirochaete-associated diarrhoea, porcine proliferative enteropathy, enzootic pneumonia and other infections where Mycoplasma is involved. There are concerns about the reported increases in the MICs of tiamulin and valnemulin for porcine Brachyspira hyodysenteriae isolates from different European countries, as only a limited number of antimicrobials are available for the treatment of swine dysentery where resistance to these antimicrobials is already common and widespread. The loss of pleuromutilins as effective tools to treat swine dysentery because of further increases in resistance or as a consequence of restrictions would present a considerable threat to pig health, welfare and productivity. In humans, only one product containing pleuromutilins (retapamulin) is authorized currently for topical use; however, products for oral and intravenous administration to humans with serious multidrug-resistant skin infections and respiratory infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA), are being developed. The objective of this review is to summarize the current knowledge on the usage of pleuromutilins, resistance development and the potential impact of this resistance on animal and human health.

Sites of feline coronavirus persistence in healthy cats.

Feline coronavirus (FCoV) is transmitted via the faecal-oral route and primarily infects enterocytes, but subsequently spreads by monocyte-associated viraemia. In some infected cats, virulent virus mutants induce feline infectious peritonitis (FIP), a fatal systemic disease that can develop in association with viraemia. Persistently infected, healthy carriers are believed to be important in the epidemiology of FIP, as they represent a constant source of FCoV, shed either persistently or intermittently in faeces. So far, the sites of virus persistence have not been determined definitely. The purpose of this study was to examine virus distribution and viral load in organs and gut compartments of specified-pathogen-free cats, orally infected with non-virulent type I FCoV, over different time periods and with or without detectable viraemia. The colon was identified as the major site of FCoV persistence and probable source for recurrent shedding, but the virus was shown also to persist in several other organs, mainly in tissue macrophages. These might represent additional sources for recurrent viraemia.

Antimicrobial resistance in equine faecal Escherichia coli isolates from North West England.

BACKGROUND: Escherichia coli isolates of equine faecal origin were investigated for antibiotic resistance, resistance genes and their ability to perform horizontal transfer. METHODS: In total, 264 faecal samples were collected from 138 horses in hospital and community livery premises in northwest England, yielding 296 resistant E. coli isolates. Isolates were tested for susceptibility to antimicrobial drugs by disc diffusion and agar dilution methods in order to determine minimum inhibitory concentrations (MIC). PCR amplification was used to detect genes conferring resistance to: ampicillin (TEM and SHV beta-lactamase), chloramphenicol (catI, catII, catIII and cml), tetracycline (tetA, tetB, tetC, tetD, tet E and tetG), and trimethoprim (dfrA1, dfrA9, dfrA12, dfrA13, dfr7, and dfr17). RESULTS: The proportion of antibiotic resistant isolates, and multidrug resistant isolates (MDR) was significantly higher in hospital samples compared to livery samples (MDR: 48% of hospital isolates; 12% of livery isolates, p < 0.001). Resistance to ciprofloxacin and florfenicol were identified mostly within the MDR phenotypes. Resistance genes included dfr, TEM beta-lactamase, tet and cat, conferring resistance to trimethoprim, ampicillin, tetracycline and chloramphenicol, respectively. Within each antimicrobial resistance group, these genes occurred at frequencies of 93% (260/279), 91%, 86.8% and 73.5%, respectively; with 115/296 (38.8%) found to be MDR isolates. Conjugation experiments were performed on selected isolates and MDR phenotypes were readily transferred. CONCLUSIONS: Our findings demonstrate that E. coli of equine faecal origin are commonly resistant to antibiotics used in human and veterinary medicine. Furthermore, our results suggest that most antibiotic resistance observed in equine E. coli is encoded by well-known and well-characterized resistant genes common to E. coli from man and domestic animals. These data support the ongoing concern about antimicrobial resistance, MDR, antimicrobial use in veterinary medicine and the zoonotic risk that horses could potentially pose to public health.

Colony Stimulating Factors in Early Feline Infectious Peritonitis Virus Infection of Monocytes and in End Stage Feline Infectious Peritonitis; A Combined In Vivo And In Vitro Approach.

Feline coronavirus (FCoV) infection initiates monocyte-associated viremia and viral persistence. Virus-infected, -activated monocytes also trigger feline infectious peritonitis (FIP), a fatal systemic disease of felids typified by granulomatous (peri)phlebitis. Currently, the exact mechanisms inducing monocyte activation and FIP are unknown. This study attempted to identify the potential immediate effect of virulent FCoV on colony-stimulating factor (CSF) (granulocyte (G)-CSF, monocyte (M)-CSF and granulocyte-monocyte (GM)-CSF levels through in vitro assessment, alongside prototypical pro- and anti-inflammatory mediators (interleukin (IL)-1, IL-6, IL-12p40, tumor necrosis factor (TNF)-α, and IL-10); this was assessed alongside the in vivo situation in the hemolymphatic tissues of cats euthanized with natural end-stage FIP. For the in vitro work, isolated monocytes from SPF cats were cultured short-term and infected with the FIP virus (FIPV) strain DF2. Mediator transcription was assessed by quantitative reverse transcriptase PCR (RT-qPCR) at 3, 6 and 9 h post infection (hpi), and in the post-mortem samples of bone marrow, spleen, and mesenteric lymph nodes (MLN) of cats with FIP. We observed limited and transient changes in cytokine transcription in monocytes after infection, i.e., a significant increase of IL-6 at 3 hpi and of GM-CSF over the 3 and 6 hpi period, whereas M-CSF was significantly decreased at 9 hpi, with a limited effect of age. The findings indicate that the infection induces expansion of the monocyte/macrophage population, which would ensure the sufficient supply of cells for consistent viral replication. In natural disease, the only upregulation was of G-CSF in the MLN, suggesting either immune exhaustion or an active downregulation by the host as part of its viral response.

Whole Genome Sequence Analysis of the First Vancomycin-Resistant Enterococcus faecium Isolates from a Libyan Hospital in Tripoli.

The purpose of the study was to investigate the molecular characteristics and genetic relatedness of the first reported cases of vancomycin-resistant enterococci (VRE) from the Tripoli Medical Center, Libya. In total, 43 VRE isolates were obtained from various clinical sites throughout the years 2013-2014, including 40 vanA-type and 2 vanB-type vancomycin-resistant Enterococcus faecium isolates and 1 vanC1-type Enterococcus gallinarum. Of the 42 E. faecium, 19 isolates were subjected to whole genome sequencing. Core genome multilocus sequence typing (cgMLST) analysis revealed three sequence clusters (SCs) of clonally related isolates, which were linked to different hospital wards. The first two VRE isolates, isolated early 2013 from patients in the medical intensive care unit, were grouped in SC1 (MLST [ST] 78, vanB) and differed in only 3 of 1423 cgMLST alleles. The SC2 (n = 16, special care baby unit, neonatal intensive care unit, pediatric surgery ward, and oncology ward) and SC3 (n = 1, antenatal ward) were all ST80 vanA-VRE, but the single SC3 isolate differed in 233 alleles compared with SC2. Within SC2, isolates differed in 1-23 alleles. Comparison with a larger database of E. faecium strains indicated that all isolates clustered within the previously defined hospital clade A1. A combination of Resfinder and mlplasmid analysis identified the presence of resistance genes on different plasmid predicted genetic elements among different SCs. In conclusion, this study documents the first isolates causing outbreaks with VRE in the Libyan health care system. Further surveillance efforts using molecular typing methods to monitor spread of multidrug-resistant bacteria in the Libyan health care system are urgently needed.

Equine airway inflammation in loose-housing management compared with pasture and conventional stabling.

Icelandic horses are often stabled in loose-housing systems, and to date this type of stabling has not been evaluated with regard to its potential impact on respiratory health. The objective was to assess if differences in management systems (eg, conventional stable, loose housing and pasture only) affect the degree of airway inflammation, evaluated by cytology of tracheal aspirate (TA) and bronchoalveolar lavage (BAL) fluid. In total, 84 Icelandic horses (aged 8.1±4.6 years) housed under three different management systems (conventional stables [n=29], loose-house systems [n=29] and pasture [n=26]) were included. Endoscopy including mucus scoring, TA and BAL was performed. TA and BAL cytologies were evaluated by performing both the total cell count (TCC) and the differential cell count (DCC). Significantly higher BAL neutrophil DCC (P=0.032, P=0.040) and TA TCC (P=0.007, P=0.028) were found for each of the two groups of horses with indoor access (conventional stable and loose housing) compared with the pasture group. Regardless of stabling environment, weak positive correlations were found between TA and BAL TCC (r=0.37, P<0.001), between TA TCC and TA neutrophil ratio (r=0.33, P=0.002), as well as between TA and BAL neutrophil ratio (r=0.39, P=<0.001). A larger proportion of horses with indoor access showed evidence of subclinical airway inflammation characterised by an increase in TA and BAL neutrophil ratios.

Age-related dynamics of pro-inflammatory cytokines in equine bronchoalveolar lavage (BAL) fluid and peripheral blood from horses managed on pasture.

The objectives of this study were to evaluate the natural age-related variation and compare the level of pro-inflammatory cytokines in the peripheral blood and lower airways of horses. The mRNA expression of IL-1ß, IL-6, IL-8 TNF-α TLR-4 in bronchoalveolar lavage (BAL) fluid and peripheral blood mononuclear cells (PBMC) were studied by quantitative real time polymerase chain reaction (PCR) and differential cell count cytology from 44 horses of different ages. A significant age-related increase was found for the mRNA expression of IL-6, IL-8, TLR-4 and TNF-α in stimulated BAL cells and for TNF-α in stimulated PBMC. Furthermore, a significant decrease was found in the mRNA expression of IL-1ß and TNF-α in stimulated BAL cells compared to stimulated PBMC. In conclusion, continued low antigen exposure of horses in the pasture environment could lead to a tight regulation of mRNA gene expression in the airway space compared to the peripheral blood and favour an age-related accumulation of mRNA genes.

A surgical approach to the lateral compartment of the equine guttural pouch in the standing horse: modification of the forgotten "Garm technique".

The objective of this study was to evaluate the feasibility, efficacy and complications following lavage and drainage of the lateral compartment (LC) of the equine guttural pouch (GP) using a modified Garm's technique (MGT). In an ex vivo study (study 1), six cadaver heads were examined to assess the anatomical limits of the surgical approach and whether vital structures might be damaged. This was followed by an in vivo study (study 2) in which a lavage/drainage tube was placed for 3 days into each LC of four standing horses using the MGT. In both studies, the procedure offered direct access into the LC and indirect access into the medial compartments of the GP. In study 1, the MGT provided a rostroventral point of access allowing drainage of the LC, with no obvious iatrogenic damage. In study 2, the MGT permitted lavage of the entire GP in three healthy horses and one horse with mild GP empyema. The only major complication was development of emphysema of the lateral wall of one LC, with secondary collapse of the mucous membrane. The time for secondary wound healing was 12-14 days. The MGT can be performed safely in standing horses and may be of value in providing access for lavage and drainage in horses with mild GP empyema.

Vancomycin-Resistant Enterococci: A Review of Antimicrobial Resistance Mechanisms and Perspectives of Human and Animal Health.

Vancomycin-resistant enterococci (VRE) are both of medical and public health importance associated with serious multidrug-resistant infections and persistent colonization. Enterococci are opportunistic environmental inhabitants with a remarkable adaptive capacity to evolve and transmit antimicrobial-resistant determinants. The VRE gene operons show distinct genetic variability and apparently continued evolution leading to a variety of antimicrobial resistance phenotypes and various environmental and livestock reservoirs for the most common van genes. Such complex diversity renders a number of important therapeutic options including "last resort antibiotics" ineffective and poses a particular challenge for clinical management. Enterococci resistance to glycopeptides and multidrug resistance warrants attention and continuous monitoring.

Environmental and public health related risk of veterinary zinc in pig production - Using Denmark as an example.

At great economic cost, important steps have been taken over the last many decades to reduce and control emissions of heavy metals in order to protect the environment and public health. Monitoring has confirmed the success of these policies with progressive declines of heavy metals in for example air, sewage sludge and environmental samples. For zinc, such improvements may nevertheless be counter-acted by its widely usage as a feed additive and veterinary medicinal product to piglets in the post-weaning period resulting in reduced occurrence of diarrhea and improvement of daily weight gain. This review therefore focuses on two major concerns associated with veterinary use of zinc, namely the quantifiable risks to the environment and promotion of (multi) resistant bacteria like LA-MRSA in pig farms. Denmark is used as an informed and realistic worst-case scenario, representing the largest pig production per capita in Europe. It is furthermore, one of the countries where most recent information can be found regarding soil monitoring data and zinc consumption within the pig production. An average increase in soil concentration by >45% was recently reported within the period 1998-2014. In order to predict future risk, this review presents new and simplified model predictions using current soil concentrations, annual load rates and predicted accumulation rates. In conclusion, it is estimated that within 25 years, continued agricultural practice of current zinc loads may result in a situation where almost all soils receiving manure from intensive piglet production may be at risk, but also other pig production types may result in scenarios with predicted risk to soil dwelling species, especially in sandy soils. Besides the quantifiable risks to soil ecosystems, high levels of zinc furthermore co-select for the persistence of LA-MRSA CC398 and other resistant bacteria on pig farms.

Occurrence, species distribution, antimicrobial resistance and clonality of methicillin- and erythromycin-resistant staphylococci in the nasal cavity of domestic animals.

beta-Lactams and macrolides are important antibiotics for treatment of staphylococcal infections in both humans and animals. The aim of the study was to investigate the occurrence, species distribution and clonality of methicillin- and erythromycin-resistant staphylococci in the nasal cavity of dogs, horses, pigs, and cattle in Denmark. Nasal swabs were collected from a total of 400 animals, including 100 individuals of each species. Methicillin- and erythromycin-resistant staphylococci were isolated on selective media, identified by 16S rDNA sequencing, and typed by pulsed field gel electrophoresis (PFGE). Methicillin-resistant coagulase-negative staphylococci (MRCoNS) harbouring mecA were isolated from horses (50%) and dogs (13%), but not from food animals. The species identified were S. haemolyticus (n=21), S. vitulinus (n=19), S. sciuri (n=13), S. epidermidis (n=8), and S. warneri (n=2). mecA-mediated methicillin resistance in S. vitulinus was described for the first time. Methicillin-resistant S. aureus was not detected. PFGE analysis revealed the presence of specific MRCoNS clones in samples originating from the same veterinary hospital or equine farm. Erythromycin-resistant S. aureus (ERSA) was detected in 38% of pigs and all isolates harboured a constitutively expressed erm(C) gene. The vast majority (37/38) of pigs carrying ERSA originated from a farm characterized by frequent use of macrolides. Most ERSA isolates (28/38) displayed indistinguishable or closely related PFGE patterns, indicating clonal distribution within the farm. Based on the analysis of data on antimicrobial consumption, the occurrence of MRCoNS in companion animals and that of ERSA in pigs reflected national and local patterns of antimicrobial usage.

Do antimicrobial mass medications work? A systematic review and meta-analysis of randomised clinical trials investigating antimicrobial prophylaxis or metaphylaxis against naturally occurring bovine respiratory disease.

A distinct difference between veterinary and human medicine is the routine use of antimicrobial mass medications (prophylaxis, metaphylaxis) to healthy individuals. The need for antimicrobial mass medications is based on beliefs that group/s of animals will contract a bacterial disease (i.e. morbidity) and/or die (i.e. mortality). Bovine respiratory disease (BRD) represents the major indication for cattle antimicrobials worldwide. The objectives were to perform a systematic review and meta-analysis of randomised controlled clinical trials (RCTs) for naturally occurring BRD investigating antimicrobial prophylaxis/metaphylaxis to prevent morbidity/mortality. In total, 58 publications met the inclusion criteria summarizing 169 individual RCTs, spanning 50 years (1966-2016). Antimicrobial prophylaxis and metaphylaxis demonstrated moderate, yet highly variable relative risk reductions in BRD morbidity. These were dependent on the antimicrobial classes used, dependent on metaphylaxis definition, BRD attack rates and duration of the RCTs. Best relative risk reductions were from broad-spectrum critically important antimicrobials, or combinations. BRD prophylaxis/metaphylaxis represents major antimicrobial consumption for highly variable short-term gains in absolute risk reduction of morbidity/mortality. Despite widespread use of prevention products, the need for antimicrobial mass medications should be re-evaluated since the underlying problem is more likely the segmented infrastructure of the feedlot and veal calf industries compared to the disease itself.

Spa typing and identification of pvl genes of meticillin-resistant Staphylococcus aureus isolated from a Libyan hospital in Tripoli.

OBJECTIVES: The purpose of the study was to investigate the molecular characteristics of meticillin-resistant Staphylococcus aureus (MRSA) isolated from clinical sources in Tripoli, Libya. METHODS: A total of 95 MRSA strains collected at the Tripoli medical Centre were investigated by spa typing and identification of the Panton-Valentine Leukocidin (pvl) genes. RESULTS: A total of 26 spa types were characterized and distributed among nine clonal complexes; CC5 (n=32), CC80 (n=18), CC8 (n=17) and CC22 (n=12) were the most prevalent clonal complexes. In total, 34% of the isolates were positive for PVL. CONCLUSIONS: This study demonstrated the presence of CA-MRSA and pvl positive strains in hospital settings and underlines the importance of using molecular typing to investigate the epidemiology of MRSA. Preventative measures and surveillance systems are needed to control and minimize the spread of MRSA in the Libyan health care system.

Natural FCoV infection: cats with FIP exhibit significantly higher viral loads than healthy infected cats.

Natural feline coronavirus (FCoV) infection has been shown to not only induce intestinal infection with viral shedding, but also systemic infection which either remains without clinical signs or leads to feline infectious peritonitis (FIP). As systemic infection is not the key event in the development of FIP, the question arises as to whether a potential difference in viral load might be of importance. Therefore, the purpose of this study was to quantitatively assess feline coronavirus (FCoV) RNA loads in haemolymphatic tissues of healthy, long-term FCoV-infected cats and cats with FIP. In cats that died from FIP, viral loads were significantly higher, indicating a higher rate of viral replication or a reduced capacity for viral clearance in cats developing and/or suffering from FIP.

Use of colistin-containing products within the European Union and European Economic Area (EU/EEA): development of resistance in animals and possible impact on human and animal health.

Since its introduction in the 1950s, colistin has been used mainly as a topical treatment in human medicine owing to its toxicity when given systemically. Sixty years later, colistin is being used as a last-resort drug to treat infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacteriaceae (e.g., Escherichia coli, Klebsiella pneumoniae), for which mortality can be high. In veterinary medicine, colistin has been used for decades for the treatment and prevention of infectious diseases. Colistin has been administered frequently as a group treatment for animal gastrointestinal infections caused by Gram-negative bacteria within intensive husbandry systems. Given the ever-growing need to retain the efficacy of antimicrobials used to treat MDR infections in humans, the use of colistin in veterinary medicine is being re-evaluated. Despite extensive use in veterinary medicine, there is limited evidence for the development of resistance to colistin and no evidence has been found for the transmission of resistance in bacteria that have been spread from animals to humans. Since surveillance for colistin resistance in animals is limited and the potential for such transmission exists, there is a clear need to reinforce systematic monitoring of bacteria from food-producing animals for resistance to colistin (polymyxins). Furthermore, colistin should only be used for treatment of clinically affected animals and no longer for prophylaxis of diseases, in line with current principles of responsible use of antibiotics.

Macrolides and lincosamides in cattle and pigs: use and development of antimicrobial resistance.

Macrolides and lincosamides are important antibacterials for the treatment of many common infections in cattle and pigs. Products for in-feed medication with these compounds in combination with other antimicrobials are commonly used in Europe. Most recently approved injectable macrolides have very long elimination half-lives in both pigs and cattle, which allows once-only dosing regimens. Both in-feed medication and use of long-acting injections result in low concentrations of the active substance for prolonged periods, which causes concerns related to development of antimicrobial resistance. Acquired resistance to macrolides and lincosamides among food animal pathogens, including some zoonotic bacteria, has now emerged. A comparison of studies on the prevalence of resistance is difficult, since for many micro-organisms no agreed standards for susceptibility testing are available. With animal pathogens, the most dramatic increase in resistance has been seen in the genus Brachyspira. Resistance towards macrolides and lincosamides has also been detected in staphylococci isolated from pigs and streptococci from cattle. This article reviews the use of macrolides and lincosamides in cattle and pigs, as well as the development of resistance in target and some zoonotic pathogens. The focus of the review is on European conditions.

Age-related changes in intracellular expression of IFN-γ and TNF-α in equine lymphocytes measured in bronchoalveolar lavage and peripheral blood.

Diseases of the lower airways represent some of the most common conditions affecting horses of all ages, but the type and severity tends to follow the horses' age. The age-related dysregulation of pro-inflammatory cytokines may, in part contribute to the development of the diseases. Therefore, we hypothesize that the expression of pro-inflammatory cytokines increases with age. Peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage (BAL) cells from clinically healthy horses of different ages were used for the investigation. The cells were stimulated and the production of IFN-γ and TNF-α measured using flow cytometry. The frequency of IFN-γ producing lymphocytes in both BAL and PBMCs from old horses was significantly increased compared to the young horses. The age-related increase of TNF-α production was also found in PBMCs but not in BAL cells. In conclusion, the productions of certain pro-inflammatory cytokine are age-associated. This age-associated increase of pro-inflammatory cytokines production may be a co-factor for the pathogenesis of equine airway diseases.

Pharmacokinetics in pulmonary epithelial lining fluid and plasma of ampicillin and pivampicillin administered to horses.

Ampicillin concentrations in pulmonary epithelial lining fluid (PELF) and plasma was studied after single intravenous ampicillin administration (15mg/kg) or single intragastric administration of its prodrug, pivampicillin (19.9mg/kg) to horses and discussed in relation to minimum inhibitory concentrations (MIC) of common equine respiratory pathogens. After intravenous administration, elimination of ampicillin was fast and not detectable in plasma after 12h in three out of six horses. Pivampicillin was absorbed well in non-fasted horses with an oral bioavailability of 36%. The degree of penetration of ampicillin into PELF, as described by the AUC(PELF)/AUC(plasma) ratio from 0 to 12h was 0.40 after intravenous administration and 1.00 after pivampicillin administration. In horses, ampicillin administered either intravenously or orally, in the form of pivampicillin, can provide clinically relevant drug concentrations in PELF for at least 12h, when treating susceptible equine respiratory pathogens (e.g. streptococci). Treatment of other bacterial pathogens requires susceptibility testing and possibly more frequent dosing, depending of minimum inhibitory concentrations (MIC) values.