Perfil fenotípico de resistência à colistina e tigeciclina em um hospital público no Brasil / Phenotypical profile of colistin and tigecycline resistance in a public hospital in Brazil / Perfil fenotípico de resistencia a la colistina y tigeciclina en un hospital público de Brasil

Justificativa e objetivos: Infecções Relacionadas à Assistência à Saúde (IRAS) causadas por bacilos Gram negativos multirresistentes (BGN-MDR) são consideradas um problema de saúde pública e um impacto nas taxas de mortalidade nas Unidades de Terapia Intensiva (UTI). O objetivo deste estudo foi verificar o perfil fenotípico de resistência à colistina e à tigeciclina, consideradas como último recurso terapêutico aos BGN-MDR. Métodos: Os dados foram coletados nas fichas de busca ativa do serviço de controle de infecções e prontuários médicos de pacientes internados em duas UTIs de um hospital público de Joinville, entre janeiro de 2016 e junho de 2017. Resultados: Ocorreram 256 IRAS por BGN, acometendo principalmente o gênero masculino (62%), com mediana de idade de 65 anos. Entre os BGN, 37% expressaram MDR; sendo as espécies mais frequentes: Klebsiella pneumoniae e (47%), Acinetobacter baumannii (23%) e Stenotrophomonas maltophilia (11%). A resistência de BGN-MDR à colistina e tigeciclina foi de 5% e de 12%, respectivamente; 5% dos isolados foram resistentes aos dois antibióticos. A taxa de óbito entre os pacientes com IRAS por BGN-MDR resistentes à colistina foi mais alta (60%) que aquelas à tigeciclina (45%). Conclusão: K. pneumoniae e A. baumannii produtores de carbapenemases, resistentes a colistina e tigeciclina prevaleceram entre os BGN-MDR, e estiveram associadas a maioria dos óbitos. Essas observações, junto com o alto uso de carbapenêmicos na terapia empírica, mostra a necessidade do uso racional de antimicrobianos.(AU)

Background and objectives: Healthcare-associated Infections (HAIs) caused by multidrug-resistant Gram-negative bacilli (GNB-MDR) are considered a public health problem and have an impact on mortality rates in Intensive Care Units (ICU). The aim of this study was to verify the phenotypic profile of resistance to colistin and tigecycline, considered as the last antimicrobial choice to treat BGNMDR infections. Methods: Data were collected on the active search records of the infection control service and medical records of patients admitted to two ICUs at a public hospital in Joinville between January 2016 and June 2017. Results: There were 256 HAIs caused by GNB, mainly affecting males (62%), with a median age of 65 years. Among GNBs, 37% expressed MDR; the most frequent species were: Klebsiella pneumoniae (47%), Acinetobacter baumannii (23%) and Stenotrophomonas maltophilia (11%). The resistance of GNB-MDR to colistin and tigecycline was 5% and 12%, respectively; 5% of the isolates were resistant to both antibiotics. The death rate among patients with HAIs caused by colistin-resistant GNB-MDR was higher (60%) than those to tigecycline (45%). Conclusion: Carbapenemase-producing K. pneumoniae and A. baumannii, resistant to colistin and tigecycline, prevailed among GNB-MDRs, and were associated with most deaths. These observations, coupled with the high use of carbapenems in empirical therapy, show the need for rational use of antimicrobials.(AU)

Justificación y objetivos: Las Infección nosocomial (IHs) causadas por bacilos Gram negativos multirresistentes (BGN-MDR) se consideran un problema de salud pública y un impacto en las tasas de mortalidad en las Unidades de Terapia Intensiva (UTI). El objetivo de este estudio fue verificar el perfil fenotípico de resistencia a la colistina ya la tigeciclina, consideradas como último recurso terapéutico a los BGN-MDR. Métodos: Los datos fueron recolectados en las fichas de búsqueda activa del servicio de control de infecciones y prontuarios médicos de pacientes internados en dos UTIs de un hospital público de Joinville, entre enero de 2016 y junio de 2017. Resultados: Ocurrieron 256 IHs por BGN, que afectan principalmente al género masculino (62%), con mediana de edad de 65 años. Entre los BGN, el 37% expresó MDR; siendo las especies más frecuentes: Klebsiella pneumoniae (47%), Acinetobacter baumannii (23%) y Stenotrophomonas maltophilia (11%). La resistencia de BGN-MDR a la colistina y tigeciclina fue del 5% y del 12%, respectivamente; 5% de los aislados fueron resistentes a los dos antibióticos. La tasa de muerte entre los pacientes con IH causadas por los BGN-MDR resistentes la colistina fue más alta (60%) que aquellas a tigeciclina (45%). Conclusión: K. pneumoniae y A. baumannii productoras de carbapenemases, resistentes la colistina y la tigeciclina, fueron más frecuentes entre los BGN-MDR y su asociación estuvo presente en la mayoría de las muertes. Estas observaciones, junto con el alto uso de carbapenems en la terapia empírica, muestran la necesidad de un uso racional de los antimicrobianos.(AU)

Detection of blaNDM-1 in Stenotrophomonas maltophilia isolated from Brazilian soil

This study reports the presence of the blaNDM-1 gene in an isolate of Stenotrophomonas maltophilia obtained from a Brazilian soil, inside an IncA/C plasmid with ~ 45 Kb. To the best of our knowledge, this is the second report in the world and the first in Brazil of NDM-producing bacterium isolated from soil.

Antimicrobial susceptibility of hospital acquired Stenotrophomonas maltophilia isolate biofilms

Abstract Aims We sought to characterize the antibiotic susceptibility of strains of Stenotrophomonas maltophilia isolated from clinical samples, and the role of Stenotrophomonas maltophilia biofilm in antibiotic resistance. Methods Fifty-one clinical Stenotrophomonas maltophilia isolates were obtained from patients with nosocomial infection in the surgical wards and ICUs of six general hospitals in Tianjin, China. In vitro models of Stenotrophomonas maltophilia biofilms were established and confirmed by scanning electron microscopy and fluorescence microscopy with silver staining. The minimal inhibitory concentrations and biofilm inhibitory concentrations of commonly used antibiotics were determined. Results 47 of 51 strains were resistant to three or more antibiotics. 42 of 51 strains formed Stenotrophomonas maltophilia biofilms in vitro. Stenotrophomonas maltophilia biofilm formation greatly reduced sensitivity to most tested antibiotics, but not to levofloxacin. However, in the presence of erythromycin scanning electron microscopy revealed that levofloxacin inhibited Stenotrophomonas maltophilia biofilm formation. Factorial ANOVA revealed that erythromycin enhanced susceptibility to levofloxacin, cefoperazone/sulbactam, and piperacillin (p < 0.05), and an ΔE model revealed that levofloxacin and erythromycin acted synergistically in biofilms, suggesting specific use of combined macrolide therapy may represent an effective treatment for Stenotrophomonas maltophilia infection. Conclusions Antibiotics could act synergistically to combat the protection conferred to clinical isolates of Stenotrophomonas maltophilia by biofilms. Macrolide antibiotics may be effective where used in combination.

Role of sul2 Gene Linked to Transposase in Resistance to Trimethoprim/Sulfamethoxazole Among Stenotrophomonas maltophilia Isolates

No abstract available.

The sul1 Gene in Stenotrophomonas maltophilia With High-Level Resistance to Trimethoprim/Sulfamethoxazole

Emerging resistance to trimethoprim/sulfamethoxazole (SXT) poses a serious threat to the treatment of Stenotrophomonas maltophilia infections. We determined the prevalence and molecular characteristics of acquired SXT resistance in recent clinical S. maltophilia isolates obtained from Korea. A total of 252 clinical isolates of S. maltophilia were collected from 10 university hospitals in Korea between 2009 and 2010. Antimicrobial susceptibility was determined by using the CLSI agar dilution method. The sul1, sul2, and sul3 genes, integrons, insertion sequence common region (ISCR) elements, and dfrA genes were detected using PCR. The presence of the sul1 gene and integrons was confirmed through sequence analysis. Among the 32 SXT-resistant isolates, sul1 was detected in 23 isolates (72%), all of which demonstrated high-level resistance (> or =64 mg/L) to SXT. The sul1 gene (varying in size and structure) was linked to class 1 integrons in 15 of the 23 isolates (65%) harboring this gene. None of the SXT-susceptible isolates or the SXT-resistant isolates with a minimum inhibitory concentration of 4 and 8 mg/L were positive for sul1. Moreover, the sul2, sul3, and dfrA genes or the ISCR elements were not detected. The sul1 gene may play an important role in the high-level SXT resistance observed in S. maltophilia.

Clinical Factors Associated with Acquisition of Resistance to Levofloxacin in Stenotrophomonas maltophilia

PURPOSE: Fluoroquinolones, rapidly gaining prominence in treatment of Stenotrophomonas maltophilia (SMP), are noted for their potency and tolerability. However, SMP may rapidly acquire resistance to fluoroquinolones. We evaluated associations of clinical factors with acquisition of levofloxacin resistance (LFr) in SMP. MATERIALS AND METHODS: Our retrospective cohort study was based on patient data collected between January 2008 and June 2010. Through screening of 1275 patients, we identified 122 patients with data for SMP antibiotic susceptibility testing in > or =3 serial SMP isolates. RESULTS: We assigned the 122 patients to either the SS group (n=54) in which levofloxacin susceptibility was maintained or the SR group (n=31) in which susceptible SMP acquired resistance. In multivariate regression analysis, exposure to levofloxacin for more than 3 weeks [odds ratio (OR) 15.39, 95% confidential interval (CI) 3.08-76.93, p=0.001] and co-infection or co-colonization with Klebsiella pneumoniae resistant to levofloxacin (OR 4.85, 95% CI 1.16-20.24, p=0.030) were independently associated with LFr acquisition in SMP. CONCLUSION: Acquisition of LFr during serial sampling of SMP was related to the levofloxacin exposure.

Smqnr VARIANTS IN CLINICAL ISOLATES OF Stenotrophomonas maltophilia IN BRAZIL / Variantes de Smqnr de isolados clínicos de Stenotrophomonas maltophilia no Brasil

SUMMARY Stenotrophomonas maltophilia contains a novel chromosomally-encoded qnr gene named Smqnr that contributes to low intrinsic resistance to quinolone. We described Smqnr in 13 clinical isolates of S. maltophilia from two Brazilian hospitals, over a 2-year period. The strains were identified by API 20 NE (bioMérieux, France). Susceptibility by microdilution method to trimetroprim/sulfamethoxazole, ciprofloxacin, levofloxacin, minocycline, ceftazidime, chloramphenicol and ticarcillin/clavulanate was performed according to CLSI. PCR detection of Smqnr gene was carried out. The sequence of Smqnr was compared with those deposited in GenBank. Pulsed-field gel electrophoresis (PFGE) of all strains was performed. Thirteen Smqnr positives isolates were sequenced and three novel variants of Smqnr were identified. All 13 Smqnr isolates had distinguishable patterns by PFGE. This is the first report of Smqnr in S. maltophilia isolated in Brazil. .

RESUMO S. maltophilia contem um novo gene qnr cromossômico denominado Smqnr que contribui para baixa resistência intrínseca a quinolonas. Descrevemos Smqnr em 13 isolados clínicos de S. maltophilia de dois hospitais brasileiros, ao longo do período de dois anos. Os isolados foram identificados pela API 20 NE (bioMérieux, França). Susceptibilidade pelo método de microdiluição dos seguintes antibióticos trimetroprim/sulfametoxazol, ciprofloxacina, levofloxacina, minociclina, ceftazidima, cloranfenicol e ticarcilina/clavulanato foi realizada segundo o CLSI. Detecção do gene de Smqnr foi realizada por PCR. A sequência de Smqnr foi comparada com aquelas depositadas no GenBank. Foi realizada eletroforese em gel de campo pulsado (PFGE) de todos os isolados. Treze isolados contendo Smqnr foram sequenciados e identificados três variantes do gene Smqnr. Todos os 13 isolados de Smqnr apresentaram diferentes padrões por PFGE. Este é o primeiro relato de Smqnr em isolados de S. maltophilia no Brasil. .

Antimicrobial Susceptibility of Stenotrophomonas maltophilia Isolates from Korea, and the Activity of Antimicrobial Combinations against the Isolates

The aim of this study was to determine antimicrobial susceptibility of recent clinical Stenotrophomonas maltophilia isolates from Korea, and to compare the activity levels of several combinations of antimicrobials. A total of 206 non-duplicate clinical isolates of S. maltophilia was collected in 2010 from 11 university hospitals. Antimicrobial susceptibility testing was performed using the Clinical Laboratory Standards Institute agar dilution method. In vitro activity of antimicrobial combinations was tested using the checkerboard method. The susceptibility rates to trimethoprim-sulfamethoxazole and minocycline were 96% and 99%, respectively. The susceptibility rate to levofloxacin was 64%. All of four antimicrobial combinations showed synergy against many S. maltophilia isolates. A combination of trimethoprim-sulfamethoxazole plus ticarcillin-clavulanate was most synergistic among the combinations. None of the combinations showed antagonistic activity. Therefore, some of the combinations may be more useful than individual drugs in the treatment of S. maltophilia infection. Further clinical studies are warranted to validate our in vitro test results.

Antimicrobial Susceptibility of Stenotrophomonas maltophilia Isolates from a Korean Tertiary Care Hospital

We determined the antimicrobial susceptibility of 90 clinical isolates of Stenotrophomonas maltophilia collected in 2009 at a tertiary care hospital in Korea. Trimethoprim-sulfamethoxazole, minocycline, and levofloxacin were active against most of the isolates tested. Moxifloxacin and tigecycline were also active and hold promise as therapeutic options for S. maltophilia infections.

Frequency of oral mucositis and microbiological analysis in children with acute lymphoblastic leukemia treated with 0.12 percent chlorhexidine gluconate

In view of the morbidity potential of oral complications in patients with leukemia, this study evaluated the clinical and microbiological alterations that occur in the oral mucosa of children with acute lymphoblastic leukemia (ALL) undergoing antineoplastic chemotherapy and prophylactic administration of 0.12 percent chlorhexidine gluconate. The sample consisted of 17 children aged 2 to 12 years that underwent clinical examination of the oral mucosa for the detection of oral lesions. In addition, biological material was collected from labial and buccal mucosa for microbiological analysis. Oral mucositis was observed in only 5 (29.4 percent) patients. Microbiological analysis revealed a reduced number of potentially pathogenic microorganisms, such as coagulase-negative staphylococci (47 percent), Candida albicans (35.3 percent), Klebsiella pneumoniae (5.9 percent), enteropathogenic Escherichia coli (5.9 percent), and Stenotrophomonas maltophilia (5.9 percent). Patients with oral mucositis showed a higher frequency of coagulase-negative staphylococci (80 percent) when compared with patients with normal oral mucosa (33.3 percent). In conclusion, the results of the present study suggest that the prophylactic use of 0.12 percent chlorhexidine gluconate reduces the frequency of oral mucositis and oral pathogens in children with ALL. In addition, the present findings suggest a possible relationship between coagulase-negative staphylococci and the development of oral mucositis.

Tendo em vista o potencial de morbidade das complicações orais em pacientes com leucemia, este estudo avaliou as alterações clínicas e microbiológicas que ocorrem na mucosa bucal de crianças com leucemia linfoblástica aguda (LLA), submetidas à quimioterapia antineoplásica e administração profilática do gluconato de clorexidina 0,12 por cento. A amostra foi constituída de 17 crianças de 2 a 12 anos, as quais foram submetidas a exame clínico da mucosa oral para a detecção de lesões bucais. Além disso, foi coletado material biológico das mucosas labial e jugal para análises microbiológicas. A mucosite oral foi observada em apenas 5 (29,4 por cento) pacientes. A análise microbiológica revelou a presença de um número reduzido de microorganismos potencialmente patogênicos, como estafilococos coagulase-negativos (47 por cento), Candida albicans (35,3 por cento), Klebsiella pneumoniae (5,9 por cento), Escherichia coli enteropatogênica (5,9 por cento) e Stenotrophomonas maltophilia (5,9 por cento). Pacientes com mucosite oral apresentaram uma maior freqüência de estafilococos coagulase-negativos (80 por cento) quando comparados aos pacientes que exibiam mucosa oral normal (33,3 por cento). Em conclusão, os resultados do presente estudo sugerem que o uso profilático do gluconato de clorexidina 0,12 por cento reduz a freqüência de mucosite oral e de patógenos orais em crianças com LLA. Além disso, os presentes achados sugerem uma possível relação entre estafilococos coagulase-negativos e o desenvolvimento de mucosite oral.

Analysis of Acquired Resistance Genes in Stenotrophomonas maltophilia / 대한진단검사의학회지

BACKGROUND: Stenotrophomonas maltophilia is a gram-negative bacillus and a nosocomial pathogen in immunocompromised patients. Trimethoprim/sulfamethoxazole (TMP/SMX) is the drug of choice for treating S. maltophilia infection; however, resistance to TMP/SMX is increasing. In this study, we investigated the relationship between the incidence of TMP/SMX resistance and the presence of sul genes and mobile elements. METHODS: A total of 120 S. maltophilia isolates were collected from 3 university hospitals between April 2007 and April 2009. Antimicrobial susceptibilities were determined using the disk diffusion method. PCR and DNA sequencing were conducted for the detection of sul1, sul2, class 1 integron, and ISCR2 element. Repetitive extragenic palindromic sequence-based PCR (REP-PCR) was carried out to evaluate the genetic relatedness. RESULTS: The TMP/SMX-resistant (R) isolates harbored a significantly higher proportion of sul1 gene and class 1 integron than TMP/SMX-susceptible (S) isolates (P<0.001). Seventeen of 28 isolates with sul1 also had a class 1 integron, but none of the isolates without sul1 had a class 1 integron. The identified gene cassettes within class 1 integrons include aacA4, aadA1, aac6'-II, and qac. None of the 120 isolates carried sul2, glmM, or ISCR2 element. REP-PCR did not show any genetic relatedness among the isolates. CONCLUSIONS: In Korea, the resistance of S. maltophilia isolates to TMP/SMX is due to sul1 within a class 1 integron rather than to sul2. The class 1 integron also harbors multiple antibiotic resistance genes in addition to sul1, and therefore it could mediate multidrug resistance in S. maltophilia.

The immunomodulatory effect of antibiotics on the secretion of tumour necrosis factor alpha by peripheral blood mononuclear cells in response to Stenotrophomonas maltophilia stimulation / Efecto inmunomodulatorio de los antibióticos sobre la secreción del factor de necrosis tumoral alfa por células sanguíneas mononucleares periféricas en respuesta a la estimulación de stenotrophomonas maltophilia

Some antibiotics have been shown to modify the host immune response. Infection with Stenotrophomonas maltophilia, is often difficult to treat due to multiresistance to antibiotics. The authors examined the effect of four commonly used antimicrobial agents (ciprofloxacin, ceftazidime, cotrimoxazole and piperacillin-tazobactam) on tumour necrosis factor alpha (TNF alpha) production by human peripheral blood mononuclear cells (PBMC) stimulated with heat-killed S maltophilia. Cotrimoxazole was the only antibiotic that suppressed TNFa secretion at clinically achievable concentrations. This may explain its use with good effect in the treatment of S maltophilia infections. However at supratherapeutic concentrations, ceftazidime and ciprofloxacin, but not piperacillin-tazobactam, also inhibited significantly the production of TNF alpha. Cotrimoxazole, in addition to its antimicrobial effect against S maltophilia, has an immunomodulatory effect on peripheral blood mononuclear cells stimulated by S maltophilia.

Algunos antibióticos han mostrado ser capaces de modificar la respuesta inmune del huésped. Las infecciones con Stenotrophomonas maltophilia – un patógeno emergente – son difíciles de tratar debido a su multiresistencia a los antibióticos. Examinamos el efecto de cuatro agentes antimicrobianos comúnmente usados (ciprofloxacina, ceftazidima, cotrimoxazol, y piperacilina-tazobactam) sobre la producción del factor de necrosis tumoral alfa (FNTa) por las células sanguíneas mononucleares periféricas humanas (PBMC) estimuladas con S maltophilia inactivadas mediante calor. El cotrimoxazol – en concentraciones clínicamente posibles – fue el único antibiótico que eliminó la secreción FNTa. Esto puede explicar su uso efectivo en el tratamiento de las infecciones por S maltophilia. Sin embargo, en concentraciones supraterapéuticas, la ceftazidima y la cipro-floxacina – pero no la piperacilina-tazobactam – también inhibieron significativamente la producción de FNTa. El cotrimoxazol, además de su efecto antimicrobiano contra S maltophilia, tiene un efecto inmuno-modulatorio sobre las células sanguíneas mononucleares periféricas estimuladas por S maltophilia.

Two Episodes of Stenotrophomonas maltophilia Endocarditis of Prosthetic Mitral Valve: Report of a Case and Review of the Literature

Stenotrophomonas maltophilia (previously named Xanthomonas maltophilia) is an aerobic, non-fermentive, Gram-negative bacillus that is wide spread in the environment. It was considered to be an organism with limited pathogenic potential, which was rarely capable of causing diseases in human other than those who were in debilitated or immunocompromised state. More recent studies have established that Stenotrophomonas maltophilia can behave as a true pathogen. Endocarditis due to this organism is rare, and only 24 cases of Stenotrophomonas maltophilia endocarditis have been reported in the medical literature. Most cases were associated with risk factors, including intravenous drug abuse, dental treatment, infected intravenous devices, and previous cardiac surgery. We present a case with two episodes of Stenotrophomonas maltophilia endocarditis after mitral valve prosthesis implantation, which was treated with antibiotics initially, and a combination of antibiotics and surgery later. To our knowledge, this is the first case of repetitive endocarditis due to Stenotrophomonas maltophilia.