Dataset Information

Dose-response relationship between antimicrobial drugs and livestock-associated MRSA in pig farming.

ABSTRACT: The farming community can be a vehicle for introduction of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in hospitals. During 2011-2013, an 18-month longitudinal study aimed at reducing the prevalence of LA-MRSA was conducted on 36 pig farms in the Netherlands. Evaluations every 6 months showed a slight decrease in MRSA prevalence in animals and a stable prevalence in farmers and family members. Antimicrobial use, expressed as defined daily dosages per animal per year, decreased 44% during the study period and was associated with declining MRSA prevalence in pigs. MRSA carriage in animals was substantially higher at farms using cephalosporins. Antimicrobial use remained strongly associated with LA-MRSA in humans regardless of the level of animal contact. A risk factor analysis outlined potential future interventions for LA-MRSA control. These results should encourage animal and public health authorities to maintain their efforts in reducing antimicrobial use in livestock and ask for future controlled intervention studies.

SUBMITTER: Dorado-Garcia A

PROVIDER: S-EPMC4451891 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Dose-response relationship between antimicrobial drugs and livestock-associated MRSA in pig farming.

Dorado-García Alejandro A Dohmen Wietske W Bos Marian E H ME Verstappen Koen M KM Houben Manon M Wagenaar Jaap A JA Heederik Dick J J DJ

Emerging infectious diseases 20150601 6

The farming community can be a vehicle for introduction of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in hospitals. During 2011-2013, an 18-month longitudinal study aimed at reducing the prevalence of LA-MRSA was conducted on 36 pig farms in the Netherlands. Evaluations every 6 months showed a slight decrease in MRSA prevalence in animals and a stable prevalence in farmers and family members. Antimicrobial use, expressed as defined daily dosages per animal per yea ...[more]

PMID: 25989456

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Project description:Previous research on methicillin susceptible Staphylococcus aureus (MSSA) belonging to livestock-associated (LA-) sequence type (ST) 398, isolated from pigs and their local surroundings, indicated that differences between these MSSA and their methicillin resistant predecessors (MRSA) are often limited to the absence of the staphylococcal cassette chromosome mec (SCCmec) and few single nucleotide polymorphisms. So far, our understanding on how LA-MRSA endure the environmental conditions associated with pig-farming as well as the putative impact of this particular environment on the mobilisation of SCCmec elements is limited. Thus, we performed in-depth genomic and transcriptomic analyses using the LA-MRSA ST398 strain IMT38951 and its methicillin susceptible descendant. We identified a mosaic-structured SCCmec region including a putative replicative SCCmecVc which is absent from the MSSA chromosome through homologous recombination. Based on our data, such events occur between short repetitive sequences identified within and adjacent to two distinct alleles of the large cassette recombinase genes C (ccrC). We further evaluated the global transcriptomic response of MRSA ST398 to particular pig-farm associated conditions, i.e., contact with host proteins (porcine serum) and a high ammonia concentration. Differential expression of global regulators involved in stress response control were identified, i.e., ammonia-induced alternative sigma factor B-depending activation of genes for the alkaline shock protein 23, the heat shock response and the accessory gene regulator (agr)-controlled transcription of virulence factors. Exposure to serum transiently induced the transcription of distinct virulence factor encoding genes. Transcription of genes reported for mediating the loss of methicillin resistance, especially ccrC, was not significantly different compared to the unchallenged controls. We concluded that, from an evolutionary perspective, bacteria may save energy by incidentally dismissing a fully replicative SCCmec element in contrast to the induction of ccr genes on a population scale. Since the genomic SCCmec integration site is a hot-spot of recombination, occasional losses of elements of 16 kb size may restore capacities for the uptake of foreign genetic material. Subsequent spread of resistance, on the other hand, might depend on the autonomous replication machinery of the deleted SCCmec elements that probably enhance chances for reintegration of SCCmec into susceptible genomes by mere multiplication.

Project description:Farm animals have been identified as an emerging reservoir for transmission of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) to humans. The low incidence of MRSA in humans and farm animals in Norway has led to the implementation of a national strategy of surveillance and control of LA-MRSA aiming to prevent livestock becoming a domestic source of MRSA to humans. In 2015, MRSA clonal complex 1 spa-type t177 was identified in nine Norwegian pig herds in two neighboring counties. An outbreak investigation was undertaken, and measures of control through eradication were imposed. We performed a register-based cohort study including pig herds and MRSA-positive persons in Norway between 2008 and 2016 to investigate the livestock-association of MRSA CC1, the transmission of the outbreak strain to humans before and after control measures, and the effect of control measures imposed. Data from the Norwegian Surveillance System of Communicable Diseases were merged with data collected through outbreak investigations for LA-MRSA, the National Registry and the Norwegian Register for Health Personnel. Whole-genome sequencing was performed on isolates from livestock and humans identified through contact tracing, in addition to t177 and t127 isolates diagnosed in persons in the same counties. It is likely that a farm worker introduced MRSA CC1 to a sow farm, and further transmission to eight fattening pig farms through trade of live pigs confirmed the potential for livestock association of this MRSA type. The outbreak strain formed a distinct phylogenetic cluster which in addition to the pig farms included one sheep herd and five exposed persons. None of the investigated isolates from possible cases without direct contact to the MRSA positive farms were phylogenetically related to the outbreak strain. Moreover, isolates of t177 or t127 from healthcare and community-acquired cases were not closely related to the outbreak cluster. Eradication measures imposed were effective in eliminating MRSA t177 from the positive pig holdings, and the outbreak strain was not detected in the national pig population or in persons from these counties after control measures.

Project description:Antimicrobial resistance (AMR) is a major public health threat, and inappropriate antimicrobial use (AMU) in food animal production can contribute to the global burden of AMR in humans. This study was conducted to understand knowledge, attitude, and practice (KAP) of smallholder livestock owners regarding antimicrobial use, residue, and resistance in three agro-ecological zones and production systems in Ethiopia. A cross-sectional study based on structured interviews was conducted. Twenty-one items were used to assess farmers' KAP. Item response theory (IRT) model and Cronbach's alpha were used to assess the KAP measurement scales. Inferential analyses were used to compare the differences in the practices in terms of the farm and socio-economic characteristics. There was a difference in the type of antimicrobials reported use between agro-ecological zones and production systems. Pastoralists most commonly used antibiotics (86.7%) followed by anthelminthics (70.8%). Overall, tetracyclines (36.4%), aminoglycosides (31.3%), and trimethoprim-sulfonamides (6.2%) were the most frequently used classes of antibiotics across the study sites. Human preparation antibiotics (tetracyclines) were also being used for veterinary purposes by 18.5% of pastoralist households. About 81.6% of livestock owners surveyed reported to have access to veterinary drugs although access varied between agro-ecological zones and production system. About 72.3% of pastoralists administered antibiotics by not following through the full treatment course. Moreover, 70% of respondents were not aware of the recommended withdrawal periods of milk and meat after antibiotic treatment. It was noticed that around 80 and 70% of respondents had a tendency to give doses higher or lower than recommended of antimicrobials, respectively. The study confirms the need for interventions to increase knowledge among smallholder farmers to improve the way antimicrobials in general and antibiotics in particular are used in these settings. In addition, professional involvement, supervision, and guidance can also lead to more efficient antimicrobial use by smallholder livestock owners. The study also highlights the need for research into the development of usable tools that measure antibiotic knowledge and attitudes.

Project description:IntroductionA one-time vancomycin loading dose of 25-30 mg/kg is recommended in the current iteration of the vancomycin consensus guidelines in order to more rapidly achieve target serum concentrations and hasten clinical improvement. However, there are few clinical data to support this practice, and the extents of its benefits are largely unknown.MethodsA multicenter, retrospective, cohort study was performed to assess the impact of a vancomycin loading dose (≥ 20 mg/kg) on clinical outcomes and rates of nephrotoxicity in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. The study matched patients in a 1:1 fashion based on age, Pitt bacteremia score, and bacteremia source. The primary outcome was composite treatment failure (30-day mortality, bacteremia duration ≥ 7 days after vancomycin initiation, persistent signs and symptoms of infection ≥ 7 days after vancomycin initiation, or switch to an alternative antimicrobial agent). Secondary outcomes included duration of bacteremia, length of stay post-bacteremia onset, and nephrotoxicity.ResultsA total of 316 patients with MRSA bacteremia were included. Median first doses in the loading dose and non-loading dose groups were 23.0 mg/kg and 14.3 mg/kg, respectively (P < 0.001). No difference was found in composite failure rates between the non-loading dose and loading dose groups (40.5% vs. 36.7%; P = 0.488) or in the incidence of nephrotoxicity (12.7% vs. 16.5%; P = 0.347). While multivariable regression modeling showed receipt of a vancomycin loading dose on a mg/kg basis was not significantly associated with composite failure [aOR 0.612, 95% CI (0.368-1.019)]; post hoc analyses demonstrated that initial doses ≥ 1750 mg were independently protective against failure [aOR 0.506, 95% CI (0.284-0.902)] without increasing the risk for nephrotoxicity [aOR 0.909, 95% CI (0.432-1.911)].ConclusionThese findings suggest that initial vancomycin doses above a certain threshold may decrease clinical failures without increasing toxicity and that weight-based dosing might not be the optimal strategy.

Dataset Information

Dose-response relationship between antimicrobial drugs and livestock-associated MRSA in pig farming.

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Dose-response relationship between antimicrobial drugs and livestock-associated MRSA in pig farming.

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