RESUMEN
Lactoferrin is an antimicrobial glycoprotein that demonstrates a broad-spectrum of activity against a wide variety of clinical pathogens. This study investigated the potential of bovine lactoferrin (bLf) against multidrug resistant Staphylococcus capitis (S. capitis) strains. Growth curve analysis and time-kill curves demonstrated that at 750 µg ml-1 lactoferrin significantly inhibited (50.6%, P < 0.05) the growth of most isolates tested (90%), and this effect was based on a bacteriostatic mechanism. At the same concentration, bLf also significantly inhibited (30%, P < 0.05) biofilm formation in 40% of strains tested. Combinations of bLf with selected antibiotics were assessed for enhanced antimicrobial activity using growth curves. BLf combined with ß-lactam antibiotics reduced the growth of S. capitis strains, however, the effects were not significant. BLf displays antimicrobial effects against multidrug resistant S. capitis isolates, but with strain-specific effects.
Asunto(s)
Antibacterianos , Biopelículas , Lactoferrina , Pruebas de Sensibilidad Microbiana , Staphylococcus capitis , Lactoferrina/farmacología , Animales , Bovinos , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Antibacterianos/farmacología , Staphylococcus capitis/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple , Infecciones Estafilocócicas/microbiologíaRESUMEN
OBJECTIVES: Fosfomycin has regained attention for treating infections caused by methicillin-resistant Staphylococcus aureus and multidrug-resistant coagulase-negative staphylococci. In this research, our objective was to investigate the mechanisms underlying fosfomycin resistance in Staphylococcus capitis. METHODS: The minimum inhibitory concentrations (MICs) of fosfomycin were assessed in 109 clinical S. capitis isolates by the agar dilution method. By cloning the fos-like genes into the shuttle vector, pTSSCm-Pcap, and observing the change in fosfomycin MICs, the gene function was verified. Core genome multilocus sequence typing and comparative genomics analysis were conducted to determine the population characteristics of S. capitis isolates and analyse the genetic environment of the fos-like genes. RESULTS: We identified a novel fosfomycin resistance gene, fosSC, on the chromosome in 58 out of 109 (53.2%) S. capitis isolates. The deduced products of the fosSC genes shared 67.15-67.88% amino acid sequence identity with FosB. The RN-pT-fosSC transformants carrying fosSC showed a 512-fold increase in the fosfomycin MICs. The fosSC gene was embedded in a conserved genetic context, but IS431mec was located to the left of the fosSC gene in cluster L due to the insertion of staphylococcal cassette chromosome mec. CONCLUSIONS: The chromosomal fosSC genes in some lineages of S. capitis explained their high-level fosfomycin resistance. Ongoing surveillance is crucial for monitoring the potential threat of horizontal transfer, which could be facilitated by the presence of mobile genetic elements surrounding the fosSC gene.
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Antibacterianos , Farmacorresistencia Bacteriana , Fosfomicina , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas , Staphylococcus capitis , Fosfomicina/farmacología , Antibacterianos/farmacología , Humanos , Infecciones Estafilocócicas/microbiología , Staphylococcus capitis/genética , Staphylococcus capitis/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Tipificación de Secuencias Multilocus , Genes Bacterianos/genéticaRESUMEN
This case report details the management of a 79-year-old male with recurrent methicillin-resistant Staphylococcus capitis bacteremia and endocarditis. The patient's clinical journey encompassed multiple hospital admissions, with challenges in managing endocarditis, pacemaker replacements, and potential cutaneous sources of infection. The treatment regimen included intravenous antibiotic therapy during hospitalization and suppressive antibiotic treatment upon discharge, alongside a decolonization strategy for his scalp lesions.
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Antibacterianos , Bacteriemia , Endocarditis Bacteriana , Staphylococcus capitis , Humanos , Masculino , Anciano , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Antibacterianos/uso terapéutico , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis Bacteriana/microbiología , Endocarditis Bacteriana/diagnóstico , Staphylococcus capitis/efectos de los fármacos , Staphylococcus capitis/aislamiento & purificación , Staphylococcus capitis/genética , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/diagnóstico , RecurrenciaRESUMEN
Due to their richness of bioactive substances, rose hips are a valuable raw material for obtaining extracts with potential antimicrobial activity. The aim of the study was to determine the antagonistic potential of whole pseudo-fruit and flesh extracts of three Rosa sp. varieties against Staphylococcus spp. bacteria isolated as food contaminants. The biological material in this study consisted of seven strains of bacteria from the genus Staphylococcus. Two strains-Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis DSMZ 3270-were used as reference strains. The other five strains were food-derived isolates-S. epidermidis A5, S. xylosus M5, S. haemolyticus M6, S. capitis KR6, and S. warneri KR2A. The material was the pseudo-fruits of Rosa canina, Rosa pomifera Karpatia, and Rosa rugosa. The polyphenols were extracted from the fleshy part and the whole pseudo-fruit for all rose varieties. The tested preparations differed significantly in their polyphenol composition. The sum of polyphenols ranged from 28â 862 to 35â 358 mg/100 g of lyophilisate. The main groups of polyphenols found in the preparations were flavanols and ellagitannins. All of the tested extracts inhibited the growth of staphylococci at a concentration of 500 mg/mL. Rosa rugosa fruit extract showed the strongest antimicrobial properties among the studied extracts. For all the strains, the growth inhibition had a diameter of 20.3-29.0 mm. Moreover, six out of the seven tested strains showed the highest inhibition with the use of this extract. The MIC of rose extracts was in the range of 3.125-500 mg/mL and was strictly dependent on the bacterial species, the species of the rose, and the part of the fruit from which the extract was obtained. Correlations were assessed between the main groups of polyphenols in the extracts and their inhibition of bacterial growth. In the case of pseudo-fruit extracts, the inhibitory effect on bacterial growth positively correlated with the content of ellagitannins, and this effect was observed for almost all the tested strains. The results presented herein follow the current trend of minimising the use of chemical preservatives in food; from this point of view, rose extracts are very promising.
Asunto(s)
Antibacterianos/química , Flavonoides/química , Taninos Hidrolizables/química , Polifenoles/química , Rosa/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Contaminación de Alimentos/prevención & control , Microbiología de Alimentos/métodos , Frutas/química , Humanos , Taninos Hidrolizables/aislamiento & purificación , Taninos Hidrolizables/farmacología , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/química , Polifenoles/aislamiento & purificación , Polifenoles/farmacología , Staphylococcus/efectos de los fármacos , Staphylococcus/crecimiento & desarrollo , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus capitis/efectos de los fármacos , Staphylococcus capitis/crecimiento & desarrollo , Staphylococcus epidermidis/efectos de los fármacos , Staphylococcus epidermidis/crecimiento & desarrollo , Staphylococcus haemolyticus/efectos de los fármacos , Staphylococcus haemolyticus/crecimiento & desarrolloRESUMEN
BACKGROUND: Methicillin-resistant staphylococcus capitis (MRSC) NRCS-A clone (Multi- resistant and vancomycin-non susceptible) has been recently described as an emerging cause of nosocomial bacteremia, especially in neonatal intensive-care units (NICUs). OBJECTIVE: The objective of this study was to evaluate the antibiotic and antiseptic resistance patterns, biofilm-producing ability and the prevalence of SCCmec and ACME types among MRSC isolates as well as to check the possible presence of NRCS-A clone at Tehran's Children's Medical Center, Iran. METHODS: A total of 256 coagulase-negative Staphylococcal isolates were collected, of which 10 S. capitis isolates were obtained and tested for susceptibility against 13 antimicrobial and 3 antiseptic agents, as well as biofilm production. The presence of 15 distinct resistance genes, staphylococcal cassette chromosome mec (SCCmec), and arginine catabolic mobile elements (ACMEs) were tracked. RESULTS: Seven out of 10 S. capitis isolates were MRSC (MIC90 van=8µg/mL) and resistant to trimethoprim/sulfamethoxazole, produced biofilm, (3 as strong biofilm producers) and carried ACME types I and II. Despite the identification of mec and ccr complexes in some isolates, all the SCCmec cassettes were untypeable (UT). CONCLUSION: According to the studied features, only one isolate belonged to the NRSC-A clone. The results indicate that MRSC with high antibiotic resistance and unknown SCCmec might become a serious problem in the future for the treatment of patients, particularly children.
Asunto(s)
Infecciones Estafilocócicas , Staphylococcus capitis , Antibacterianos/farmacología , Niño , Células Clonales/efectos de los fármacos , Humanos , Recién Nacido , Irán/epidemiología , Resistencia a la Meticilina/efectos de los fármacos , Resistencia a la Meticilina/genética , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/epidemiología , Staphylococcus capitis/efectos de los fármacosRESUMEN
Rapidly evolving multidrug resistance renders conventional antimicrobial strategies increasingly inefficient. This urges the exploration of alternative strategies with a lower potential of resistance development to control microbial infections. A promising option is antimicrobial photodynamic therapy (aPDT), especially in the setting of wound infections. In this study its effectiveness was tested as a treatment option for polymicrobially infected wounds in both in vitro and in vivo models. First, aPDT was applied to wound-relevant Gram-positive and Gram-negative bacteria in planktonic culture as the standard in vitro test system and compared different media to show a possible dependency of the therapy on the surrounding environment. In a second step, aPDT was investigated in an in vitro model mimicking the wound bed conditions using fibrin-coated culture plates. Finally, we tested aPDT in vivo in a polymicrobial infected wound healing model in immunocompromised BALB/c mice. In vitro, it was shown that the bactericidal effectiveness of aPDT was strongly dependent on the surrounding environment of the phototoxic reaction. In vivo, the significant delay in wound healing induced by polymicrobial infection was drastically diminished by a two-times application of aPDT using 100 µM methylene blue (generally regarded as safe for topical application on human skin) and 24 J cm-2 pulsed red LED light. Our experiments suggest that aPDT is capable of significantly improving wound healing also in complicated polymicrobially infected wound situations.
Asunto(s)
Antibacterianos/farmacología , Coinfección/tratamiento farmacológico , Coinfección/microbiología , Modelos Animales de Enfermedad , Escherichia coli K12/efectos de los fármacos , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Staphylococcus capitis/efectos de los fármacos , Animales , Antibacterianos/química , Femenino , Técnicas In Vitro , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Fármacos Fotosensibilizantes/síntesis química , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Introduction. Linezolid-resistant (LZR) Staphylococcus capitis has recently emerged in our hospital, and its potential resistance mechanisms are still not clear.Aim. This study aimed to investigate the epidemiology, clinical and genetic characteristics, resistance mechanisms and biofilm formation capacity of LZR S. capitis isolated from patients at Huashan Hospital, Shanghai, PR China between 2012 and 2018.Methodology. Strains were subjected to antimicrobial susceptibility testing (AST) with antibiotics using the broth microdilution method according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The presence of cfr, optrA and poxtA, as well as mutations in the 23S ribosomal (r)RNA and ribosomal proteins, was investigated using PCR and sequencing techniques. The genetic relationship between isolates was analysed using pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS). Biofilm biomasses were detected by using crystal violet staining.Results. Twenty-one LZR S. capitis strains displayed MICs of 32-512 µg ml-1. All LZR strains showed G2576T and C2104T mutations in the 23S rRNA V region. Besides G2576T and C2104T, no base mutations were detected in the V region. The cfr was detected in 12 strains, while optrA and poxtA were not amplified in 21 S. capitis strains. PFGE showed that the LZR S. capitis strains belonged to a single clone. The phylogenetic tree showed that 20 LZR S. capitis strains were highly similar to LNZR-1, isolated from Harbin (located in the north of China) in 2013, which showed resistance to linezolid.Conclusions. In this research, cfr-negative strains displayed linezolid MICs of 32 µg ml-1. In comparison, cfr-positive strains exhibited linezolid MICs of 128-512 µg ml-1, indicating that high levels of linezolid resistance appear to be related to the presence of cfr. The outbreak of LZR S. capitis in our hospital needs to be monitored closely.
Asunto(s)
Antibacterianos/farmacología , Linezolid/farmacología , Infecciones Estafilocócicas/epidemiología , Staphylococcus capitis/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Biopelículas/crecimiento & desarrollo , China/epidemiología , ADN Bacteriano/aislamiento & purificación , Farmacorresistencia Bacteriana/genética , Electroforesis en Gel de Campo Pulsado , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mutación , Oxazolidinonas/farmacología , ARN Ribosómico 23S/genética , Infecciones Estafilocócicas/microbiología , Staphylococcus capitis/genética , Staphylococcus capitis/fisiología , Secuenciación Completa del Genoma , Adulto JovenRESUMEN
To increase the knowledge about S. capitis in the neonatal setting, we conducted a nationwide 3-month survey in 38 neonatal intensive care units (NICUs) covering 56.6% of French NICU beds. We demonstrated 14.2% of S. capitis BSI (S.capBSI) among nosocomial BSIs. S.capBSI incidence rate was 0.59 per 1000 patient-days. A total of 55.0% of the S.capBSIs were late onset catheter-related BSIs. The S. capitis strains infected preterm babies (median gestational age 26 weeks, median birth weight 855 g). They were resistant to methicillin and aminoglycosides and belonged to the NRCS-A clone. Evolution was favorable in all but one case, following vancomycin treatment.
Asunto(s)
Sepsis/epidemiología , Infecciones Estafilocócicas/epidemiología , Staphylococcus capitis/aislamiento & purificación , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones Relacionadas con Catéteres/tratamiento farmacológico , Infecciones Relacionadas con Catéteres/epidemiología , Infecciones Relacionadas con Catéteres/etiología , Farmacorresistencia Bacteriana Múltiple , Femenino , Francia/epidemiología , Humanos , Recién Nacido , Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal , Masculino , Sepsis/tratamiento farmacológico , Sepsis/etiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/etiología , Staphylococcus capitis/efectos de los fármacosRESUMEN
The multidrug-resistant Staphylococcus capitis NRCS-A clone is responsible for sepsis in preterm infants in neonatal intensive care units (NICUs) worldwide. Here, to retrace the spread of this clone and to identify drivers of its specific success, we investigated a representative collection of 250 S. capitis isolates from adults and newborns. Bayesian analyses confirmed the spread of the NRCS-A clone and enabled us to date its emergence in the late 1960s and its expansion during the 1980s, coinciding with the establishment of NICUs and the increasing use of vancomycin in these units, respectively. This dynamic was accompanied by the acquisition of mutations in antimicrobial resistance- and bacteriocin-encoding genes. Furthermore, combined statistical tools and a genome-wide association study convergently point to vancomycin resistance as a major driver of NRCS-A success. We also identified another S. capitis subclade (alpha clade) that emerged independently, showing parallel evolution towards NICU specialization and non-susceptibility to vancomycin, indicating convergent evolution in NICU-associated pathogens. These findings illustrate how the broad use of antibiotics can repeatedly lead initially commensal drug-susceptible bacteria to evolve into multidrug-resistant clones that are able to successfully spread worldwide and become pathogenic for highly vulnerable patients.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Sepsis Neonatal/microbiología , Staphylococcus capitis/efectos de los fármacos , Staphylococcus capitis/genética , Adulto , Teorema de Bayes , Francia , Genes Bacterianos/genética , Genoma Bacteriano , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Pruebas de Sensibilidad Microbiana , Mutación , Fenotipo , Polimorfismo de Nucleótido Simple , Recombinación Genética , Infecciones Estafilocócicas/microbiología , Staphylococcus capitis/aislamiento & purificación , Staphylococcus capitis/patogenicidad , Vancomicina/uso terapéuticoRESUMEN
This study compared changes in antimicrobial susceptibilities and molecular characteristics of coagulase-negative staphylococci (CNS) between the year 2000 and the year 2014-2015 to evaluate the policy of separating drug prescribing and dispensing in Korea. We obtained 68 CNS clinical isolates from two tertiary general hospitals before (the year 2000; n = 25) and after (the year 2014 - 2015; n = 43) implementation of the separation. Isolates were identified as Staphylococcus capitis, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, and Staphylococcus warneri. When minimal inhibitory concentrations of 14 antimicrobials were applied to isolates, resistance rates to gentamicin and oxacillin in 2000 were significantly higher than in 2014-2015 (p < 0.05). Fifty-seven isolates were methicillin-resistant CNS (MR-CNS), 42 of which were also multidrug resistant; overall, multidrug resistance decreased from 72% in the year 2000 to 55.8% in 2014-2015. Staphylococcal cassette chromosome mec (SCCmec) type III was the dominant type of MR-CNS in the year 2000, while SCCmec type IV was the dominant type in 2014-2015. Twenty-five sequence types (STs) were identified; ST2 appeared most frequently in both periods. After 15 years of implementation of this policy, multidrug resistance as well as methicillin and gentamicin resistance in CNS decreased, but not resistance to other antibiotics. Long-term surveillance at both genotypic and phenotypic levels of various species is necessary for further evaluation of this policy.
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Antibacterianos/farmacología , Prescripciones de Medicamentos/estadística & datos numéricos , Farmacorresistencia Bacteriana Múltiple/genética , Infecciones Estafilocócicas/epidemiología , Staphylococcus epidermidis/genética , Staphylococcus haemolyticus/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Coagulasa/deficiencia , Coagulasa/genética , Expresión Génica , Gentamicinas/farmacología , Humanos , Legislación de Medicamentos , Pruebas de Sensibilidad Microbiana , Oxacilina/farmacología , Filogenia , República de Corea/epidemiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus , Staphylococcus capitis/clasificación , Staphylococcus capitis/efectos de los fármacos , Staphylococcus capitis/genética , Staphylococcus capitis/aislamiento & purificación , Staphylococcus epidermidis/clasificación , Staphylococcus epidermidis/efectos de los fármacos , Staphylococcus epidermidis/aislamiento & purificación , Staphylococcus haemolyticus/clasificación , Staphylococcus haemolyticus/efectos de los fármacos , Staphylococcus haemolyticus/aislamiento & purificación , Staphylococcus hominis/clasificación , Staphylococcus hominis/efectos de los fármacos , Staphylococcus hominis/genética , Staphylococcus hominis/aislamiento & purificación , Staphylococcus saprophyticus , Centros de Atención TerciariaRESUMEN
The skin microbiota is thought to play a key role in host protection from infection. Nisin J is a novel nisin variant produced by Staphylococcus capitis APC 2923, a strain isolated from the toe web space area in a screening study performed on the human skin microbiota. Whole-genome sequencing and mass spectrometry of the purified peptide confirmed that S. capitis APC 2923 produces a 3,458-Da bacteriocin, designated nisin J, which exhibited antimicrobial activity against a range of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and Cutibacterium acnes The gene order in the nisin J gene cluster (nsjFEGBTCJP) differs from that of other nisin variants in that it is lacking the nisin regulatory genes, nisRK, as well as the nisin immunity gene nisI Nisin J has 9 amino acid changes compared to prototypical nisin A, with 8 amino acid substitutions, 6 of which are not present in other nisin variants (Ile4Lys, Met17Gln, Gly18Thr, Asn20Phe, Met21Ala, Ile30Gly, Val33His, and Lys34Thr), and an extra amino acid close to the C terminus, rendering nisin J the only nisin variant to contain 35 amino acids. This is the first report of a nisin variant produced by a Staphylococcus species and the first nisin producer isolated from human skin.IMPORTANCE This study describes the characterization of nisin J, the first example of a natural nisin variant, produced by a human skin isolate of staphylococcal origin. Nisin J displays inhibitory activity against a wide range of bacterial targets, including MRSA. This work demonstrates the potential of human commensals as a source for novel antimicrobials that could form part of the solution to antibiotic resistance across a broad range of bacterial pathogens.
Asunto(s)
Nisina/genética , Nisina/metabolismo , Piel/microbiología , Staphylococcus capitis/metabolismo , Antiinfecciosos/farmacología , Humanos , Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Familia de Multigenes/genética , Nisina/efectos de los fármacos , Propionibacteriaceae/efectos de los fármacos , Propionibacteriaceae/genética , Propionibacteriaceae/metabolismo , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Staphylococcus capitis/efectos de los fármacos , Staphylococcus capitis/genética , Secuenciación Completa del GenomaRESUMEN
One hundred human-derived coagulase negative staphylococci (CoNS) were screened for antimicrobial activity using agar-based deferred antagonism assays with a range of indicator bacteria. Based on the findings of the screen and subsequent well assays with cell free supernatants and whole cell extracts, one strain, designated CIT060, was selected for further investigation. It was identified as Staphylococcus capitis and herein we describe the purification and characterisation of the novel bacteriocin that the strain produces. This bacteriocin which we have named capidermicin was extracted from the cell-free supernatant of S. capitis CIT060 and purified to homogeneity using reversed-phase high performance liquid chromatography (RP-HPLC). Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometric (MS) analysis revealed that the capidermicin peptide has a mass of 5,464 Da. Minimal inhibitory concentration (MIC) experiments showed that capidermicin was active in the micro-molar range against all the Gram-positive bacteria that were tested. Antimicrobial activity was retained over a range of pHs (2-11) and temperatures (10-121°C x 15 mins). The draft genome sequence of S. capitis CIT060 was determined and the genes predicted to be involved in the biosynthesis of capidermicin were identified. These genes included the predicted capidermicin precursor gene, and genes that are predicted to encode a membrane transporter, an immunity protein and a transcriptional regulator. Homology searches suggest that capidermicin is a novel member of the family of class II leaderless bacteriocins.
Asunto(s)
Bacteriocinas/biosíntesis , Staphylococcus capitis/metabolismo , Secuencia de Aminoácidos , Antibacterianos/farmacología , Bacteriocinas/análisis , Bacteriocinas/química , Secuencia de Bases , Cromatografía de Fase Inversa , Genoma Bacteriano , Humanos , Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Sistemas de Lectura Abierta , Conformación Proteica , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Infecciones Estafilocócicas/microbiología , Staphylococcus capitis/efectos de los fármacos , Staphylococcus capitis/genética , Secuenciación Completa del GenomaRESUMEN
Emergence of a genetically distinct, multidrug-resistant Staphylococcus capitis clone (NRCS-A) present in neonatal intensive care units has recently been extensively reported. The aims of the present study were to investigate which clones of S. capitis isolated from blood in a Swedish neonatal intensive care unit (NICU) have been present since 1987 and to investigate whether the NRCS-A clone has disseminated in Sweden. All S. capitis isolates from blood cultures of neonates (≤ 28 days of age) between 1987 and 2017 (n = 46) were whole-genome sequenced, and core genome multilocus sequence typing (cgMLST) was performed. Single-nucleotide polymorphism (SNP)-based phylogenetic relationships between the S. capitis isolates and in silico predictions of presence of genetic traits specific to the NRCS-A clone were identified. Furthermore, antibiotic susceptibility testing, including screening for heterogeneous glycopeptide-intermediate resistance, was performed. Thirty-five isolates clustered closely to the isolates previously determined as belonging to the NRCS-A clone and had fewer than 81 core genome loci differences out of 1063. Twenty-one of these isolates were multidrug resistant. The NRCS-A clone was found in 2001. Six pairs of isolates had differences of fewer than two SNPs. Genetic traits associated with the NRCS-A clone such as nsr, ebh, tarJ, and CRISPR were found in all 35 isolates. The increasing incidence of S. capitis blood cultures of neonates is predominantly represented by the NRSC-A clone at our NICU in Sweden. Furthermore, there were indications of transmission between cases; adherence to basic hygiene procedures and surveillance measures are thus warranted.
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Bacteriemia/microbiología , Genoma Bacteriano/genética , Infecciones Estafilocócicas/microbiología , Staphylococcus capitis/genética , Staphylococcus capitis/aislamiento & purificación , Antibacterianos/farmacología , Bacteriemia/epidemiología , Farmacorresistencia Bacteriana Múltiple , Genes Bacterianos/genética , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Pruebas de Sensibilidad Microbiana , Filogenia , Polimorfismo de Nucleótido Simple/genética , Infecciones Estafilocócicas/epidemiología , Staphylococcus capitis/clasificación , Staphylococcus capitis/efectos de los fármacos , Suecia/epidemiologíaRESUMEN
Antibiotic resistance crisis occasioned by sporadic appearance of multi-drug resistance (MDR) in human pathogens to clinically applied antimicrobials is a serious threat to global health. In this study, we investigated the drug resistant phenotype of Gram-positive cocci isolates from environment. Staphylococcus capitis and Staphylococcus haemolyticus colonies were isolated on mannitol-salt agar plates supplemented with tetracycline. Antibiotic susceptibility profile of the isolates via minimum inhibitory concentration (MIC) determination was examined. Isolates showed decreased sensitivity to clinically applied antimicrobial agents: tetracycline, kanamycin, erythromycin, norfloxacin, teicoplanin, and ampicillin. Genomic analysis demonstrated the presence of multiple antibiotic resistant genes in these bacteria, suggesting the origin of the multiple antimicrobials resistant phenotype. Tetracycline resistance of these isolates was transduced to Staphylococcus aureus-RN4220 strain. These findings indicate the presence of multiple antimicrobials resistant S. capitis and S. haemolyticus strain in a non-hospital setting. Moreover, the presence of plethora of genes responsible for MDR suggest that these strains could present potential threat to human health by serving as reservoir for lateral transference of antimicrobial resistance conferring foreign genetic elements to other clinically relevant pathogens.
Asunto(s)
Farmacorresistencia Bacteriana Múltiple , Staphylococcus capitis/aislamiento & purificación , Staphylococcus haemolyticus/aislamiento & purificación , Secuenciación Completa del Genoma/métodos , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Composición de Base , Coagulasa/metabolismo , Tamaño del Genoma , Pruebas de Sensibilidad Microbiana , Staphylococcus capitis/efectos de los fármacos , Staphylococcus capitis/genética , Staphylococcus haemolyticus/efectos de los fármacos , Staphylococcus haemolyticus/genéticaRESUMEN
Background: Once present in a neonatal intensive care unit (NICU), multidrug resistant Staphylococcus capitis NRCS-A is able to settle and diffuse. Objective: The objective of this study was to evaluate the impact of infection control (IC) interventions to reduce the spread of Staphylococcus capitis NRCS-A in a NICU. Methods: Between December 2012 and December 2017, all patients presenting positive sampling (blood, skin or catheter) to S. capitis were included, and clinical data were recorded from electronic clinical charts. The IC team has continually implemented measures of control infections (hand hygiene, standard precautions, patient contact isolation and disinfection of the inanimate environment). From May 2015, a steam cleaner was implemented in the cleaning procedure instead of disinfectant to disinfect heating tables and incubators. Four periods were determined: Period 1 (P1) before steam cleaner acquisition; Period 2 (P2) after implementation steam cleaner; Period 3 (P3) when the steam cleaner had broken down, and Period 4 (P4) when the steam cleaner was functional again. The consumption of antibiotics and the epidemiology of infections inside the NICU were investigated during the study period. Results: During the studied period, 37 infants were infected or colonized by S. capitis. The incidences of infection or colonization by S. capitis were P1 = 1.04, P2 = 0.55, P3 = 3.95 and P4 = 0 and were significantly different between P1-P3 and P2-P4 (p < 0.001). During the different periods, antibiotics consumption and bacterial epidemiology of the ward were stable. Conclusions: The use of steam vapor system was associated with a significantly decreased incidence of S. capitis NRCS-A infection or colonization and could constitute an effective and safe procedure to control and eradicate its diffusion inside NICUs.
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Antibacterianos/uso terapéutico , Infección Hospitalaria/prevención & control , Control de Infecciones/instrumentación , Infecciones Estafilocócicas/prevención & control , Staphylococcus capitis/aislamiento & purificación , Antibacterianos/farmacología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Farmacorresistencia Bacteriana Múltiple , Registros Electrónicos de Salud , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Control de Infecciones/métodos , Unidades de Cuidado Intensivo Neonatal , Masculino , Aislamiento de Pacientes , Infecciones Estafilocócicas/epidemiología , Staphylococcus capitis/efectos de los fármacos , VaporRESUMEN
Heteroresistance to vancomycin (HRV) represents a decreased susceptibility to vancomycin and is frequently observed in multidrug-resistant coagulase-negative staphylococci. The clinical significance of such heteroresistance is controversial, but several failures of vancomycin therapy have been related to HRV, especially in the neonatal population. Here we report the case of a preterm neonate, born at 26 weeks of gestation, who developed sepsis due to a multidrug-resistant HRV Staphylococcuscapitis isolate. Bacteremia persisted despite adequate vancomycin serum concentration and catheter removal. The patient finally recovered after replacing vancomycin by linezolid. Through this case report, we would like to alert clinicians of the potential clinical impact of HRV and to discuss the lack of therapeutic alternatives in neonates.
Asunto(s)
Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus capitis/efectos de los fármacos , Resistencia a la Vancomicina , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Humanos , Recién Nacido , Recien Nacido Prematuro , Linezolid/uso terapéutico , MasculinoRESUMEN
BACKGROUND: In neonatal intensive care units (NICUs), nosocomial late-onset sepsis (LOS), mostly due to coagulase negative staphylococci, constitute a major cause of death or impairment. Staphylococcus capitis, usually considered as a poorly virulent species, has been reported as a cause of LOS. OBJECTIVES: To review data regarding S. capitis neonatal LOS and the features of isolates involved. SOURCES: PubMed was searched up to August 2018 to retrieve studies on the topic; the keywords used were 'S. capitis', 'neonate', 'neonatal ICU', 'bloodstream infection' and 'late onset sepsis'. CONTENT: Published data highlight the worldwide endemicity of a single S. capitis clone, named NRCS-A, specifically involved in LOS. NRCS-A harbours a multidrug resistance profile (including resistance to the usual first-line antibiotics used in NICUs). It is also able to adapt under vancomycin selective pressure that could confer an advantage for its implantation and dissemination in NICUs where this selective pressure is high. Moreover, a severe morbidity has been observed in NRCS-A-related LOS. The NICU environment, and especially incubators, constitute reservoirs of NRCS-A from which it could diffuse inside the setting. Finally, the virulome and resistome of S. capitis NRCS-A contain many genes potentially implicated in its specific epidemiology and pathophysiology, including the gene nsr that may be involved in its fitness and implantation in neonatal gut flora. IMPLICATIONS: S. capitis must be considered as a true pathogen in neonates. The decreased susceptibility to vancomycin may be involved in failure of vancomycin therapy. Further studies are needed to better manage its diffusion inside each NICU but also worldwide.
Asunto(s)
Unidades de Cuidado Intensivo Neonatal , Sepsis/microbiología , Infecciones Estafilocócicas/microbiología , Staphylococcus capitis/genética , Staphylococcus capitis/patogenicidad , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Humanos , Recién Nacido , Sepsis/tratamiento farmacológico , Sepsis/fisiopatología , Sepsis/transmisión , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/fisiopatología , Infecciones Estafilocócicas/transmisión , Staphylococcus capitis/efectos de los fármacos , Vancomicina/farmacología , Vancomicina/uso terapéutico , Virulencia/genéticaRESUMEN
Coagulase-negative staphylococci (CoNS) represent one of the major causes of health care- and medical device-associated infections. Emerging antimicrobial resistance has complicated the treatment of systemic infections caused by CoNS. Here, we describe the prevalence of antimicrobial resistance in clinical CoNS strains from a tertiary care hospital over a 4-year period, and we observed a significant increase in resistance to daptomycin. Notably, Staphylococcus capitis accounted for the majority of these daptomycin-resistant (DAP-R) CoNS. To further investigate the mechanisms of daptomycin resistance in CoNS, daptomycin-susceptible clinical strains of S. capitis and Staphylococcus epidermidis underwent in vitro daptomycin exposure to generate DAP-R CoNS mutants. Unlike that seen with Staphylococcus aureus, alteration of cell surface charge was not observed in the DAP-R CoNS strains, but biofilm formation was compromised. Whole-genome sequencing analysis of the DAP-R CoNS strains identified single nucleotide polymorphisms (SNPs) in walKR, the essential two-component regulatory system controlling cell wall biogenesis. PCR and sequencing of walK and walR from 17 DAP-R CoNS clinical isolates identified seven nonsynonymous mutations. The results were confirmed by the recreation of the walK SNP in S. epidermidis, which resulted in reduced susceptibility to daptomycin and vancomycin. This study highlights the significance of CoNS in evolving daptomycin resistance and showed that walKR is shared among the staphylococcal species and is involved in antibiotic resistance development. Notably, we did not observe mutations in genes responsible for phospholipid biosynthesis or an altered cell surface charge, suggesting that reduced daptomycin susceptibility in CoNS may emerge in a fashion distinct from that in S. aureus.
Asunto(s)
Antibacterianos/farmacología , Daptomicina/farmacología , Farmacorresistencia Bacteriana/genética , Staphylococcus capitis/genética , Staphylococcus epidermidis/genética , Sustitución de Aminoácidos/genética , Proteínas Bacterianas/genética , Biopelículas/crecimiento & desarrollo , Infección Hospitalaria/microbiología , Histidina Quinasa/genética , Humanos , Pruebas de Sensibilidad Microbiana , Polimorfismo de Nucleótido Simple/genética , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Staphylococcus capitis/efectos de los fármacos , Staphylococcus capitis/aislamiento & purificación , Staphylococcus epidermidis/efectos de los fármacos , Staphylococcus epidermidis/aislamiento & purificación , Centros de Atención Terciaria , Vancomicina/farmacologíaRESUMEN
Coagulase-negative staphylococci (CoNS), such as Staphylococcus capitis, are major causes of bloodstream infections in neonatal intensive care units (NICUs). Recently, a distinct clone of S. capitis (designated S. capitis NRCS-A) has emerged as an important pathogen in NICUs internationally. Here, 122 S. capitis isolates from New Zealand (NZ) underwent whole-genome sequencing (WGS), and these data were supplemented with publicly available S. capitis sequence reads. Phylogenetic and comparative genomic analyses were performed, as were phenotypic assessments of antimicrobial resistance, biofilm formation, and plasmid segregational stability on representative isolates. A distinct lineage of S. capitis was identified in NZ associated with neonates and the NICU environment. Isolates from this lineage produced increased levels of biofilm, displayed higher levels of tolerance to chlorhexidine, and were multidrug resistant. Although similar to globally circulating NICU-associated S. capitis strains at a core-genome level, NZ NICU S. capitis isolates carried a novel stably maintained multidrug-resistant plasmid that was not present in non-NICU isolates. Neonatal blood culture isolates were indistinguishable from environmental S. capitis isolates found on fomites, such as stethoscopes and neonatal incubators, but were generally distinct from those isolates carried by NICU staff. This work implicates the NICU environment as a potential reservoir for neonatal sepsis caused by S. capitis and highlights the capacity of genomics-based tracking and surveillance to inform future hospital infection control practices aimed at containing the spread of this important neonatal pathogen.
Asunto(s)
Farmacorresistencia Bacteriana Múltiple/genética , Sepsis Neonatal/microbiología , Staphylococcus capitis/genética , Antibacterianos/farmacología , Coagulasa/genética , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Genómica/métodos , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Sepsis Neonatal/tratamiento farmacológico , Nueva Zelanda , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus capitis/efectos de los fármacosRESUMEN
OBJECTIVE: Compare the in vitro efficacy of hypochlorous acid 0.01% (HA), povidone iodine 5% (PI), chlorhexidine gluconate 4% (CHG), and isopropyl alcohol 70% (IPA) against common skin microorganisms. MATERIALS AND METHODS: Time-kill studies were conducted against methicillin-susceptible Staphylococcus aureus (MSSA) and Staphylococcus epidermidis (MSSE), methicillin-resistant S. aureus (MRSA) and S. epidermidis (MRSE), Candida albicans, Corynebacterium species (striatum and amycolatum), Propionibacterium acnes, Pseudomonas aeruginosa, Streptococcus pyogenes, Staphylococcus capitis, and Staphylococcus xylosus. RESULTS: Methicillin-resistant S. aureus: Bactericidal effect was immediate for HA and IPA. For PI and CHG, the effect occurred at 1 and 10 minutes, respectively. Methicillin-resistant S. epidermidis: Hypochlorous acid, IPA, and PI had immediate bactericidal effects, whereas CHG required 1 minute. Methicillin-susceptible Staphylococcus aureus: All agents had bactericidal effects at 1 minute. C. species, S. pyogenes, P. aeruginosa, and P. acnes: All antiseptics demonstrated immediate bactericidal effects. Methicillin-susceptible Staphylococcus epidermidis and S. capitis: Hypochlorous acid and IPA had immediate effect, whereas PI and CHG required 1 minute. C. albicans: Hypochlorous acid, IPA, and PI were immediately bactericidal, whereas CHG required 1 minute. S. xylosus: Hypochlorous acid and CHG were immediately bactericidal, whereas IPA and PI required 1 and 2 minutes, respectively. CONCLUSION: In vitro studies of HA 0.01% were observed to have equal or more efficacious antiseptic properties compared with IPA, CHG, and PI. Future studies will be needed to investigate its role in periocular use.