Emergence of trimethoprim resistance gene dfrG in Staphylococcus aureus causing human infection and colonization in sub-Saharan Africa and its import to Europe

Nurjadi, Dennis; Olalekan, Adesola; Layer, Franziska; Shittu, Adebayo; Alabi, Abraham; Ghebremedhin, Beniam; Schaumburg, Frieder; Hofmann-Eifler, Jonas; Genderen, Perry J.J. van; Caumes, Éric; Fleck, Ralf; Mockenhaupt, Frank P.; Herrmann, Mathias; Kern, Winfried V.; Abdulla, Salim; Grobusch, Martin P.; Kremsner, Peter G.; Wolz, Christiane; Zanger, Philipp

doi:10.1093/jac/dku174

Cited by 88 publications

(88 citation statements)

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“…Nevertheless, this finding is reassuring given widespread use of TMP-SXT, especially among HIV-infected children, in Botswana 36 and since high rates of TMP-SXT resistance have been reported elsewhere in SSA. 37,38 Low levels of TMP/SXT resistance is consistent with data from high-income countries demonstrating that communityacquired strains of MRSA, containing the staphylococcal cassette chromosome mec (SCCmec) type IV, are more likely to be TMP-SXT susceptible versus other SCCmec types. 39,40 Further research is warranted to determine whether TMP-SXT may have a protective effect on S. aureus nasal colonization when used as Pneumocystis jirovecii prophylaxis among HIV-infected children.…”

Section: Discussionsupporting

confidence: 78%

Prevalence of Staphylococcus aureus Nasal Carriage in Human Immunodeficiency Virus–Infected and Uninfected Children in Botswana: Prevalence and Risk Factors

et al. 2017

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Abstract. Staphylococcus aureus is an important cause of morbidity and mortality in children in sub-Saharan Africa (SSA). A major risk factor for staphylococcal infection is S. aureus colonization of the anterior nares. We sought to define risk factors for S. aureus carriage and characterize antimicrobial resistance patterns in children in Botswana. A cross-sectional study was conducted at two clinical sites in southern Botswana. Patients under 18 years of age underwent two nasal swabs and brief interviews, 4 weeks apart. Standard microbiological techniques were used. For persistent carriers, S. aureus was isolated from swabs at both time points, and for intermittent carriers, S. aureus was isolated from only one swab. Poisson regression with robust variance estimator was used to compare prevalence of carriage and the resistance phenotypes. Among 56 enrollees, prevalence of S. aureus colonization was 55% (N = 31), of whom 42% (N = 13) were persistent carriers. Of human immunodeficiency virus-infected children, 64% (N = 9) were carriers. Risk factors for nasal carriage included a history of tuberculosis (prevalence ratio [PR] = 1.60; 95% confidence interval [CI] = 1.02, 2.51; P = 0.040) and closer proximity to health care (PR = 0.89; 95% CI = 0.80, 0.99; P = 0.048). Prior pneumonia was more common among persistent rather than intermittent carriers (PR = 2.64; 95% CI = 1.64, 4.23; P < 0.001). Methicillin-resistant S. aureus (MRSA) prevalence was 13%. Of isolates tested, 16% were resistant to three or more drugs (N = 7/44). In summary, children in southern Botswana are frequently colonized with S. aureus. Antibiotic resistance, especially MRSA, is also widespread. Antibiotic recommendations for treatment of staphylococcal infections in SSA should take cognizance of these resistance patterns.

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Section: Discussionsupporting

confidence: 78%

Prevalence of Staphylococcus aureus Nasal Carriage in Human Immunodeficiency Virus–Infected and Uninfected Children in Botswana: Prevalence and Risk Factors

et al. 2017

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“…Isolates for which there was no amplification of the acquired dfr genes were subsequently analysed for their intrinsic dfrB gene [10]. The following isolates were used as positive controls: ANG880 for dfrA, ANG17A for dfrG, and FVL88.1 for dfrK.…”

Section: Detection Of Tmp Resistance Genesmentioning

confidence: 99%

“…Although resistance to SXT among clinical S. aureus isolates is rare in North America [4,5], high levels of resistance have been observed among MRSA isolates in Latin America (up to 100%) [6,7], in Asia, namely, in Taiwan (89%) and China (21%) [8], and more recently in Africa (up to 55% of colonizing and 72% of clinical S. aureus isolates) [9][10][11][12][13]. In Europe, the resistance is generally low [14]; Portugal is one exception and S. aureus SXT resistance has reached 67% [15,16].…”

Section: Introductionmentioning

confidence: 99%

“…TMP resistance is associated with two genetic mechanisms [10]: (i) acquired resistance genes (dfrA, dfrG and dfrK) located on mobile genetic elements; and (ii) mutations on the chromosomal DHFR gene (dfrB). The former resistance mechanism mediates high-level resistance to TMP (MIC ≥ 512 μg/mL), while the mutation in the intrinsic dfrB gene confers intermediate-level resistance (MIC ≤ 256 μg/mL).…”

Section: Introductionmentioning

confidence: 99%

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Frequent occurrence of trimethoprim-sulfamethoxazole hetero-resistant Staphylococcus aureus isolates in different African countries

Coelho

Lencastre

Aires-de-Sousa

2017

Eur J Clin Microbiol Infect Dis

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High rates of trimethoprim/sulfamethoxazole (SXT) resistance, a combination of two antifolate antibiotics trimethoprim (TMP) and sulfamethoxazole (SMZ), have been reported among Staphylococcus aureus isolates in Portuguese-speaking African countries. Our study aimed to evaluate the occurrence of TMP resistance markers in major SXT methicillin-resistant S. aureus (MRSA) clones from these countries. We accessed also different fitness traits that could explain the success of these isolates over the Brazilian MRSA (the most successful SXT MRSA clone worldwide but never identified in these countries). Minimum inhibitory concentrations for SXT, TMP and SMZ were determined, and genes encoding TMP resistance (dfrG, dfrA, dfrK and dfrB) were searched. Representatives of the Brazilian clone and of the major MRSA African clones were evaluated for their fitness by individual growth curves, competition assays, survival under desiccation, autolytic activity, resistance to oxidative stress, and also growth at high osmolarity and in acid and alkaline environments. Although all African isolates showed high-level resistance to TMP, the majority presented hetero-resistance to SXT. TMP resistance was linked to the presence of dfrG (78%), dfrA (19%) or both (3%) genes. Compared to the Brazilian clone, the African isolates showed higher growth rates and autolytic activity, and better survival to desiccation and alkaline conditions. Since isolates exhibiting SXT hetero-resistance are frequent in Africa, the implementation of standardized guidelines to detect this phenomenon is of major interest. The predominant MRSA clones in Portuguese-speaking African countries likely possess significant advantages over other clones, such as the Brazilian MRSA, that may explain their epidemiological success.

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“…Já os casos de MRSA recentemente descritos, que não estiveram associados a contato direto ou indireto com instituições de saúde, frequentemente apresentam resistência apenas para a classe dos beta-lactâmicos (ADCOCK et al, 1998;HEROLD et al, 1998 (WEIGEL, 2003;KADLEC et al, 2012;ARGUDÍN et al, 2014;NURJADI et al, 2014;GHANBARI et al, 2016).…”

Section: Perfil De Resistência Aos Demais Antimicrobianosunclassified

<b>Estudo da diversidade molecular de linhagens de <i>Staphylococcus aureus</i> de isolados de mastite bovina</b>

Abreu¹

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sendo os três mais frequentes t605 (57,45%), t002 (8,4%) e t127 (8,13%). Não houve associação entre a distribuição dos spa tipos e as variáveis analisadas de ano, estado, município e fazenda, e perfil de resitência aos antibicrobianos. Este é o primeiro estudo que utiliza o spa typing para avaliar uma coleção temporalmente diversa e, portanto, representativa da região estudada ao longo de 22 anos. Logo, espera-se que a descrição dos tipos de S. aureus obtidos contribua para a compreensão dos aspectos epidemiológicos envolvidos na transmissão do patógeno e do papel dos hospedeiros como reservatórios para linhagens resistentes. Tal compreensão é imprescindível para a prevenção, controle e tratamento da mastite bovina.Palavras Chaves: Staphylococcus aureus, mastite, antibiograma, mecA, spa Typing. Bovine mastitis is considered the disease of greatest impact in global dairy industry. Despite the adoption of management practices to minimize its occurrence, the results are not satisfactory for the control of Staphylococcus aureus, the major causative agent. Besides veterinary importance, there are also implications for human health due to the extensive use of antibiotics in treatment and control of the disease and due to the potential for zoonotic spread of S. aureus.The main concern regarding antimicrobial resistance is methicillin resistance mediated by the mecA gene. Molecular epidemiology studies are important for the understanding of the genetic diversity of the causative agents of mastitis. Typing by sequencing of a single locus of the X region gene of the S. aureus protein A (spa Typing) has been successfully used to investigate population structure. This project aims to investigate the antimicrobial susceptibility profile and the presence of methicillin resistance genes in S. aureus isolated from bovine mastitis, in addition to understanding the genetic diversity, identifying possible new profiles and knowing the distribution of these isolates. The results obtained to the present were the absence of methicillin resistance in the antibiogram, confirmed by the absence of mecA gene, and the low prevalence of multidrug resistance to antimicrobials. Even though resistance to at least one antibiotic was present in more than 58,74% of the isolates (242/412), ampicillin resistance corresponds to 53.64% (221/412). Different spa types were determined, the three most frequent being t605 (57.45%), t002 (8.4%) and t127 (8.13%). There was no association between the spa type distribution and the variables of year, state, municipality, farm, and antibiotic resistance profile analyzed. This is the first study that uses spa Typing to evaluate a collection as temporarily diverse and representative of the region studied in 22 years. Therefore, it is expected that the results of this study, by allowing comparison of the profile of S. aureus from different sources (animals and property), will contribute to the understanding of the epidemiological aspects involved in the transmission of the pathogen and the role of hosts as reservoi...

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Emergence of trimethoprim resistance gene dfrG in Staphylococcus aureus causing human infection and colonization in sub-Saharan Africa and its import to Europe

Cited by 88 publications

References 35 publications

Prevalence of Staphylococcus aureus Nasal Carriage in Human Immunodeficiency Virus–Infected and Uninfected Children in Botswana: Prevalence and Risk Factors

Prevalence of Staphylococcus aureus Nasal Carriage in Human Immunodeficiency Virus–Infected and Uninfected Children in Botswana: Prevalence and Risk Factors

Frequent occurrence of trimethoprim-sulfamethoxazole hetero-resistant Staphylococcus aureus isolates in different African countries

<b>Estudo da diversidade molecular de linhagens de <i>Staphylococcus aureus</i> de isolados de mastite bovina</b>

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