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Neuro- and nephrotoxicity of polymyxins are known but clinical studies in horses are lacking. The aim of this study was to describe neurogenic and nephrogenic side effects of hospitalized horses receiving Polymyxin B (PolyB) as part of their treatment plan. Twenty horses diagnosed with surgical colic (n = 11), peritonitis (n = 5), typhlocolitis (n = 2), pneumonia, and pyometra (each n = 1) were included. Antimicrobial treatment was randomized to GENTA (gentamicin 10 mg/kg bwt q24 h IV, penicillin 30.000 IU/kg q6 h IV) or NO GENTA (marbofloxacin 2 mg/kg bwt q24 h IV, penicillin 30.000 IU/kg q6 h IV). The duration of PolyB treatment ranged from 1 to 4 days. Clinical and neurological examinations were performed, and serum PolyB concentrations were measured daily during and three days following PolyB treatment. Urinary analysis, plasma creatinine, urea and SDMA were assessed every other day. Video recordings of neurological examinations were graded by three blinded observers. All horses showed ataxia during PolyB treatment in both groups (median maximum ataxia score of 3/5, range 1–3/5). Weakness was detected in 15/20 (75%) horses. In 8/14 horses, the urinary γ-glutamyltransferase (GGT)/creatinine ratio was elevated. Plasma creatinine was mildly elevated in 1/16 horses, and SDMA in 2/10 horses. Mixed-model analysis showed a significant effect of time since last PolyB dose (p = 0.0001, proportional odds: 0.94) on the ataxia score. Ataxia and weakness should be considered as reversible adverse effects in hospitalized horses receiving PolyB. Signs of tubular damage occurred in a considerable number of horses; therefore, the nephrotoxic effect of polymyxins should be considered and urinary function monitored.

Alternative lifestyles are likely to be associated with distinct usage of specific medicinal products. Our goal was to find out whether the intake of antibiotics during pregnancy and by children differs according to whether the mothers have alternative or conventional lifestyles. Therefore, we investigated the use of antibiotics by pregnant women and by children up to 11 years of age participating in the KOALA Birth Cohort Study. This cohort comprises two recruitment groups of mother–infant pairs, one with alternative lifestyles (selected via organic food shops, anthroposophic clinicians and midwives, anthroposophic under-five clinics, Rudolf Steiner schools and relevant magazines, n = 491) the other with conventional lifestyles (no selection based on lifestyle, n = 2343). Mothers in the alternative lifestyle group more frequently adhered to specific living rules and identified themselves with anthroposophy more than mothers in the conventional lifestyle group. The results revealed significant differences in antibiotic use during pregnancy and in children from 3 months to 10 years of age between the two groups. The rate of antibiotic use in children was consistently lower in the alternative lifestyle group than in the conventional lifestyle group. Antibiotic use in pregnancy was higher in low educated women, and maternal antibiotic use during lactation was higher after an instrumented delivery in hospital. Antibiotic use in the infant was higher when they had older sibs or were born in hospital, and lower in those who had been longer breastfed. After adjustment for these factors, the differences in antibiotic use between the alternative and conventional groups remained. The results suggest that an alternative lifestyle is associated with cautious antibiotic use during pregnancy, lactation and in children.

AIMS: This study aimed to characterize 79 Cutibacterium acnes strains isolated from prosthetic joint infections (PJIs) originated from eight European hospitals.METHODS: Isolates were phylotyped according to the single-locus sequence typing (SLST) scheme. We evaluated the ability of the biofilm formation of C. acnes strains isolated from PJIs and 84 isolates recovered from healthy skin. Antibiotic susceptibility testing of planktonic and biofilm cells of PJI isolates and skin isolates was performed.RESULTS: Most of the isolates from PJIs belonged to the SLST class H/phylotype IB (34.2%), followed by class D/phylotype IA1 (21.5%), class A/phylotype IA1 (18.9%), and class K/phylotype II (13.9%). All tested isolates were biofilm producers; no difference in biofilm formation was observed between the healthy skin group and the PJI group of strains. Planktonic and sessile cells of C. acnes remained highly susceptible to a broad spectrum of antibiotics, including beta-lactams, clindamycin, fluoroquinolones, linezolid, rifampin, and vancomycin. The minimal inhibitory concentrations (MICs) for planktonic and biofilm states coincided in most cases. However, the minimal biofilm eradication concentration (MBEC) was high for all antimicrobial drugs tested (>32 mg/L), except for rifampin (2 mg/L).CONCLUSIONS: C. acnes strains isolated from healthy skin were able to produce biofilm to the same extent as isolates recovered from PJIs. All C. acnes strains in planktonic and sessile states were susceptible to most antibiotics commonly used for PJI treatment, although rifampin was the only antimicrobial agent able to eradicate C. acnes embedded in biofilm.

Temocillin is active against Gram-negative bacteria, including many extended-spectrum β-lactamase (ESBL)-producing Enterobacterales. We studied its pharmacokinetics in plasma and ascitic fluid after intravenous administration of a loading dose of 2 g over 30 min, followed by continuous infusion of 6 g/24 h, to 19 critically-ill patients with septic shock associated with complicated intra-abdominal infection. We established a pharmacokinetic model describing unbound temocillin concentrations in plasma and ascitic fluid and performed Monte-Carlo simulations to evaluate the probability of target attainment (PTA) of unbound concentrations (100% fT > MIC, i.e., unbound concentrations remaining above the MIC during 100% of the time) for the applied and hypothetical dosing regimens. The temocillin AUC in ascitic fluid was 46% of the plasma AUC. Plasma unbound concentrations were best described by a two-compartment model, and an additional compartment was added to describe unbound concentration in ascitic fluid, with renal clearance as a covariate. Dosing simulations showed that 90% PTA was achieved in the plasma with the current dosing regimen for MIC ≤ 16 mg/L (EUCAST susceptibility breakpoint) but not in the ascitic fluid if renal clearance was ≥40 mL/min. Hypothetical dosing with a higher (a) loading dose or (b) infused dose allowed to reach target concentrations in ascitic fluid (a) more rapidly or (b) sustainably, but these simulations need to be evaluated in the clinics for safety and efficacy.

Biofilm virulence is mainly based on its bacterial cell surrounding biofilm matrix, which contains a scaffold of exopolysaccharides, carbohydrates, proteins, lipids, and nucleic acids. Targeting these nucleid acids or proteins could enable an efficient biofilm control. Therefore, the study aimed to test the effect of deoxyribonuclease I (DNase I) and proteinase K on oral biofilms. Six-species biofilms (Streptococcus mutans, Streptococcus oralis, Actinomyces oris, Fusobacterium nucleatum, Veillonella dispar, and Candida albicans) were exposed to DNase I (0.001 mg/mL, 0.002 mg/mL) or proteinase K (0.05 mg/mL, 0.1 mg/mL) for 1 h during biofilm formation. After 64 h, biofilms were harvested, quantified by culture analysis and visualized by image analysis using CLSM (confocal laser scanning microscopy). Statistical analysis was performed by ANOVA, followed by the Tukey test at a 5% significance level. The biofilm treatment with proteinase K induced a significant increase of Logs10 counts in S. mutans and a decrease in C. albicans, while biofilm thickness was reduced from 28.5 μm (control) to 9.07 μm (0.05 mg/mL) and 7.4 μm (0.1 mg/mL). Treatment with DNase I had no effect on the total bacterial growth within the biofilm. Targeting proteins of biofilms by proteinase K are promising adjunctive tool for biofilm control.

Mycoplasma bovis is an important pathogen causing mostly pneumonia in calves and mastitis in dairy cattle. In the absence of an effective vaccine, antimicrobial therapy remains the main control measure. Antimicrobial use in veal calves is substantially higher than in conventional herds, but whether veal calves also harbor more resistant M. bovis strains is currently unknown. Therefore, we compared antimicrobial susceptibility test results of M. bovis isolates from different cattle sectors and genomic clusters. The minimum inhibitory concentration of nine antimicrobials was determined for 141 Belgian M. bovis isolates (29 dairy, 69 beef, 12 mixed, 31 veal farms), and was used to estimate the epidemiological cut-off. Acquired resistance was frequently observed for the macrolides, while no acquired resistance to oxytetracycline and doxycycline, minimal acquired resistance to florfenicol and tiamulin, and a limited acquired resistance to enrofloxacin was seen. M. bovis isolates from beef cattle or genomic cluster III had higher odds of being gamithromycin-resistant than those from dairy cattle or genomic clusters IV and V. In this study, no cattle industry could be identified as source of resistant M. bovis strains. A single guideline for antimicrobial use for M. bovis infections, with a small remark for gamithromycin, is likely sufficient.

Antibiotic resistance (ABR) is a major threat to public health, and the majority of antibiotics are prescribed in the outpatient setting, especially in primary care. Monitoring antibiotic consumption is one key measure in containing ABR, but Swiss national surveillance data are limited. We conducted a retrospective cross-sectional study to characterise the patterns of antibiotic prescriptions, assess the time trends, and identify the factors associated with antibiotic prescribing in Swiss primary care. Using electronic medical records data, we analysed 206,599 antibiotic prescriptions from 112,378 patients. Based on 27,829 patient records, respiratory (52.1%), urinary (27.9%), and skin (4.8%) infections were the commonest clinical indications for antibiotic prescribing. The most frequently prescribed antibiotics were broad-spectrum penicillins (BSP) (36.5%), fluoroquinolones (16.4%), and macrolides/lincosamides (13.8%). Based on the WHO AWaRe classification, antibiotics were 57.9% Core-Access and 41.7% Watch, 69% of which were quinolones and macrolides. Between 2008 and 2020, fluoroquinolones and macrolides/lincosamides prescriptions significantly declined by 53% and 51%, BSP prescriptions significantly increased by 54%. Increasing patients&rsquo, age, volume, and employment level were significantly associated with antibiotic prescribing. Our results may inform future antibiotic stewardship interventions to improve antibiotic prescribing.

The vast majority of medicines in pig rearing are administered via oral group medication through medicated feed and drinking water. However, relevant on-farm factors affecting the concentration of these drugs in feed and drinking water, such as the homogeneity, stability, and cross-contamination, are largely unknown. To characterize these factors, samples of medicated feed and drinking water were taken on 24 Belgian pig farms during treatment and 2 days thereafter, as well as at different on-farm sampling sites from production to feeding troughs or drinking nipples. The samples contained amoxicillin, doxycycline, florfenicol, or flubendazole. Additionally, a questionnaire was completed. In contrast to the results of medicated feed, results of medicated water showed a large between-farm variation in antimicrobial drug concentration. The therapeutic concentration range was only met in 2 out of 11 farms using medicated feed, and in 3 out of 13 farms using medicated water. Medicated feed concentrations were often below the therapeutic concentration range mentioned in the Summary of Product Characteristics, while drinking water concentrations were just as often above as they were below the advised target concentration range. Drug residues measured 2 days after the end of therapy with both feed and water medication rarely exceeded 1% of the lowest therapeutic concentration. This study demonstrates that recommendations on good clinical practices for oral group medication in the pig industry are highly needed.

Companion animals have been described as potential reservoirs of antimicrobial resistance (AMR), however data remain scarce. Therefore, the objectives were to describe antimicrobial usage (AMU) in dogs and cats in three European countries (Belgium, Italy, and The Netherlands) and to investigate phenotypic AMR. A questionnaire and one fecal sample per animal (n = 303) were collected over one year and AMU was quantified using treatment incidence (TI). Phenotypic resistance profiles of 282 Escherichia coli isolates were determined. Nineteen percent of the animals received at least one antimicrobial treatment six months preceding sampling. On average, cats and dogs were treated with a standard daily dose of antimicrobials for 1.8 and 3.3 days over one year, respectively. The most frequently used antimicrobial was amoxicillin-clavulanate (27%). Broad-spectrum antimicrobials and critically important antimicrobials for human medicine represented 83% and 71% of the total number of treatments, respectively. Resistance of E. coli to at least one antimicrobial agent was found in 27% of the isolates. The most common resistance was to ampicillin (18%). Thirteen percent was identified as multidrug resistant isolates. No association between AMU and AMR was found in the investigated samples. The issue to address, regarding AMU in companion animal, lies within the quality of use, not the quantity. Especially from a One-Health perspective, companion animals might be a source of transmission of resistance genes and/or resistant bacteria to humans.

C-reactive protein (CRP) point-of-care testing (POCT) is increasingly being promoted to reduce diagnostic uncertainty and enhance antibiotic stewardship. In primary care, respiratory tract infections (RTIs) are the most common reason for inappropriate antibiotic prescribing, which is a major driver for antibiotic resistance. We systematically reviewed the available evidence on the impact of CRP-POCT on antibiotic prescribing for RTIs in primary care. Thirteen moderate to high-quality studies comprising 9844 participants met our inclusion criteria. Meta-analyses showed that CRP-POCT significantly reduced immediate antibiotic prescribing at the index consultation compared with usual care (RR 0.79, 95%CI 0.70 to 0.90, p = 0.0003, I2 = 76%) but not during 28-day (n = 7) follow-up. The immediate effect was sustained at 12 months (n = 1). In children, CRP-POCT reduced antibiotic prescribing when CRP (cut-off) guidance was provided (n = 2). Meta-analyses showed significantly higher rates of re-consultation within 30 days (n = 8, 1 significant). Clinical recovery, resolution of symptoms, and hospital admissions were not significantly different between CRP-POCT and usual care. CRP-POCT can reduce immediate antibiotic prescribing for RTIs in primary care (number needed to (NNT) for benefit = 8) at the expense of increased re-consultations (NNT for harm = 27). The increase in re-consultations and longer-term effects of CRP-POCT need further evaluation. Overall, the benefits of CRP-POCT outweigh the potential harms (NNTnet = 11). ispartof: ANTIBIOTICS-BASEL vol:9 issue:9 ispartof: location:Switzerland status: published

Vibrio species are a significant causative of mass mortality in mariculture worldwide, which can quickly accumulate in live food and transmit into the larval gut. With restrictions on the use of antibiotics in aquaculture, finding a proper solution to reduce the risk of Vibriosis is vital. This study aimed to evaluate the susceptibility of Vibrio harveyi, V. campbellii, V. anguillarum, and V. parahaemolyticus to twenty-six bacterial and yeast strains and use the beneficial ones to enrich live food (Branchiopod, Artemia franciscana, rotifer, Brachionus plicatilis and copepod, Tigriopus japonicus). Thus, a modified disk diffusion method was applied. After a susceptibility assay, the bacteria and yeast beneficial in suppressing the Vibrio species were labeled by fluorescent stain and used to measure the accumulation potential in different live foods. Also, the beneficial bacteria and yeast were used to enrich live foods, and then the count of loaded Vibrio was estimated after 5, 10, 15, and 20 h by the serial dilution method. From the total bacteria and yeast strains that were used, Candida parapsilosis, Pseudoalteromonas flavipulchra, Lactobacillus sakei, Bacillus natto, and B. amyloliquefaciens inhibited all four Vibrio species. The results of microbial labeling showed that L. sakei in Artemia, C. parapsilosis in rotifers, and V. harveyi in copepods had the highest accumulation rate. The results of the estimation of loaded Vibrio in different live foods also showed that the use of beneficial bacteria and yeast each significantly reduced the count of Vibrio. Application of bacteria and yeast to suppress pathogenic Vibrio maybe a sustainable method for preventing this pathogen from harmfully invading aquaculture and may also aid in reducing the chances of antibiotic resistance in pathogenic Vibrio.

Enrofloxacin is frequently administered via drinking water for the treatment of colibacillosis in broiler chickens. However, the EMA/CVMP has urged to re-evaluate historically approved doses, especially for antimicrobials administered via drinking water. In response, the objectives of this study were two-fold. First, to evaluate the pharmacokinetics (PK) of enrofloxacin following IV, PO and drinking water administration. Second, to predict the efficacy of a range of doses in the drinking water for the treatment of APEC infections. For the first objective, PK parameters were estimated by fitting a one-compartmental model with a zero-order IV infusion and an oral absorption lag function to the simultaneously modelled IV and PO data. After fixing these parameter values, a drinking behaviour pharmacokinetic (DBPK) model was developed for the description and prediction of drinking water PK profiles by adding three model improvements (different diurnal and nocturnal drinking rates, inter-animal variability in water consumption and taking account of dose non-proportionality). The subsequent simulations and probability of target attainment (PTA) analysis predicted that a dose of 12.5 mg/kg/24 h is efficacious in treating colibacillosis with an MIC up to 0.125 μg/mL (ECOFF), whereas the currently registered dose (10 mg/kg/24 h) reaches a PTA of 66% at ECOFF.

Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) among animals and humans are a public health threat. This study analyzed the occurrence of ESBL-E in a high-risk environment in a companion animal clinic and two animal patients’ households. In an intensive care unit (ICU), rectal swabs from 74 dogs and cats, 74 hand swabs from staff and 298 swabs from surfaces were analyzed for ESBL-E. Seventeen hospitalized patients (23%) and ten (3%) surfaces in the ICU tested ESBL-E positive. Transmission chains for Klebsiella pneumoniae ST307 blaCTX-M-15 and Escherichia coli ST38 blaCTX-M-14, ST88 blaCTX-M-14 and ST224 blaCTX-M-1 were observed over extended periods of time (14 to 30 days) with similar strains isolated from patients and the clinical environment. After discharge, two colonized dogs (dogs 7 and 12) and their household contacts were resampled. Dog 7 tested repeatedly positive for 77 days, dog 12 tested negative, six (24%) surfaces in the household of the persistently colonized dog tested ESBL-E positive. The owner of dog 7 and one of the owners of dog 12 were colonized. Based on whole genome sequencing, isolates from the owners, their dogs and other ICU patients belonged to the same clusters, highlighting the public health importance of ESBL-E in companion animal clinics.

The present study aims to assess the initial bacterial adhesion and biofilm formation on different aligner materials. A total of four different aligner materials, CA-medium (CAM), copolyester (COP), Duran (DUR), Erkodur (ERK), were tested. Stimulated human saliva was obtained from six healthy volunteers. Salivary bacteria were harvested by centrifugation, and 1 mL of the salivary suspension was injected onto each sample surface for 2 h and 3 days, respectively. The samples were then washed twice with 5 mL 0.9% NaCl solution, and non-adherent bacteria were removed. The adherent microorganisms were dislodged from the sample surfaces after ultrasonication for 4 min in 1 mL 0.9% NaCl on ice. After the incubation of the adherent salivary bacteria under both aerobic and anaerobic conditions on Columbia blood agar plates at 37 &deg, C and 5% CO2 and in anaerobic jars overnight, several dilutions thereof were used for the determination of CFUs. This protocol was applied three times, obtaining an average of nine independent measurements for each material group. Overall, the differences between the tested aligner materials as well as between the materials and controls were not of statistical significance (p &gt, 0.05). Regarding initial bacterial attachment and biofilm formation, the tested aligner materials are comparable to enamel and metal orthodontic brackets and can be therefore considered for clinical use. The four tested aligner materials CAM, COP, DUR, ERK showed no significant differences in initial microbial attachment and biofilm formation of aerobic and anaerobic species compared to enamel and conventional brackets.