RESUMEN
Infections caused by Staphylococcus aureus pose a significant global public problem. Therefore, new antibiotics and therapeutic strategies are needed to combat this pathogen. This investigation delves into the effects of iclaprim, a newly discovered inhibitor of folic acid synthesis, on S. aureus virulence. The phenotypic and genotypic effects of iclaprim were thoroughly examined in relation to virulence factors, biofilm formation, and dispersal, as well as partial virulence-encoding genes associated with exoproteins, adherence, and regulation in S. aureus MW2, N315, and ATCC 25923. Then, the in vivo effectiveness of iclaprim on S. aureus pathogenicity was explored by a Galleria mellonella larvae infection model. The use of iclaprim at sub-inhibitory concentrations (sub-MICs) resulted in a reduction of α-hemolysin (Hla) production and a differential effect on the activity of coagulase in S. aureus strains. The results of biofilm formation and eradication assay showed that iclaprim was highly effective in depolymerizing the mature biofilm of S. aureus strains at concentrations of 1 MIC or greater, however, inhibited the biofilm-forming ability of only strains N315 and ATCC 25923 at sub-MICs. Interestingly, treatment of strains with sub-MICs of iclaprim resulted in significant stimulation or suppression of most virulence-encoding genes expression. Iclaprim did not affect the production of δ-hemolysin or staphylococcal protein A (SpA), nor did it impact the total activity of proteases, nucleases, and lipases. In vivo testing showed that sub-MICs of iclaprim significantly improves infected larvae survival. The present study offered valuable insights towards a better understating of the influence of iclaprim on different strains of S. aureus. The findings suggest that iclaprim may have potential as an anti-virulence and antibiofilm agent, thus potentially mitigating the pathogenicity of S. aureus and improving clinical outcomes associated with infections caused by this pathogen. KEY POINTS: ⢠Iclaprim effectively inhibits α-hemolysin production and biofilm formation in a strain-dependent manner and was an excellent depolymerizing agent of mature biofilm ⢠Iclaprim affected the mRNA expression of virulence-encoding genes associated with exoproteins, adherence, and regulation ⢠In vivo study in G. mellonella larvae challenged with S. aureus exhibited that iclaprim improves larvae survival.
Asunto(s)
Antibacterianos , Biopelículas , Larva , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas , Staphylococcus aureus , Factores de Virulencia , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/patogenicidad , Staphylococcus aureus/genética , Biopelículas/efectos de los fármacos , Animales , Factores de Virulencia/genética , Antibacterianos/farmacología , Virulencia/efectos de los fármacos , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Larva/microbiología , Mariposas Nocturnas/microbiología , Proteínas Hemolisinas/genética , Ácido Fólico/farmacología , Ácido Fólico/biosíntesis , Antagonistas del Ácido Fólico/farmacología , Coagulasa/metabolismo , Modelos Animales de Enfermedad , PirimidinasRESUMEN
BACKGROUND: Coagulase-negative Staphylococcus species are an emerging cause of intramammary infection, posing a significant economic and public health threat. The aim of this study was to assess the occurrence of coagulase-negative Staphylococcus species in bovine milk and dairy farms in Northwestern Ethiopia and to provide information about their antibiotic susceptibility and virulence gene profiles. METHODS: The cross-sectional study was conducted from February to August 2022. Coagulase-negative Staphylococcus species were isolated from 290 milk samples. Species isolation and identification were performed by plate culturing and biochemical tests and the antimicrobial susceptibility pattern of each isolate was determined by the Kirby-Bauer disc diffusion test. The single-plex PCR was used to detect the presence of virulent genes. The STATA software version 16 was used for data analysis. The prevalence, proportion of antimicrobial resistance and the number of virulent genes detected from coagulase-negative Staphylococcus species were analyzed using descriptive statistics. RESULTS: Coagulase-negative Staphylococcus species were isolated in 28.6%, (95% CI: 23.5-34.2) of the samples. Of these, the S. epidermidis, S. sciuri, S. warneri, S. haemolyticus, S. simulans, S. chromogens, S. cohnii, and S. captis species were isolated at the rates of 11, 5.2, 3.4, 3.1, 3.1, 1, 1, and 0.7% respectively. All the isolates showed a high percentage (100%) of resistance to Amoxicillin, Ampicillin, and Cefotetan and 37.5% of resistance to Oxacillin. The majority (54.2%) of coagulase-negative isolates also showed multidrug resistance. Coagulase-negative Staphylococcus species carried the icaD, pvl, mecA, hlb, sec, and hla virulent genes at the rates of 26.5%, 22.1%, 21.7%, 9.6%, 9.6% and 8.4% respectively. CONCLUSION: The present study revealed that the majority of the isolates (54.2%) were found multidrug-resistant and carriage of one or more virulent and enterotoxin genes responsible for intramammary and food poisoning infections. Thus, urgent disease control and prevention measures are warranted to reduce the deleterious impact of coagulase-negative species. To the best of our knowledge, this is the first study in Ethiopia to detect coagulase-negative Staphylococcus species with their associated virulent and food poisoning genes from bovine milk.
Asunto(s)
Antibacterianos , Coagulasa , Pruebas de Sensibilidad Microbiana , Leche , Staphylococcus , Animales , Leche/microbiología , Bovinos , Staphylococcus/genética , Staphylococcus/efectos de los fármacos , Staphylococcus/aislamiento & purificación , Staphylococcus/enzimología , Etiopía , Coagulasa/genética , Coagulasa/metabolismo , Estudios Transversales , Antibacterianos/farmacología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/veterinaria , Virulencia/genética , Factores de Virulencia/genética , Femenino , Genes Bacterianos/genética , Mastitis Bovina/microbiologíaRESUMEN
Bacterial adhesins are cell-surface proteins that anchor to the cell wall of the host. The first stage of infection involves the specific attachment to fibrinogen (Fg), a protein found in human blood. This attachment allows bacteria to colonize tissues causing diseases such as endocarditis. The study of this family of proteins is hence essential to develop new strategies to fight bacterial infections. In the case of the Gram-positive bacterium Staphylococcus aureus, there exists a class of adhesins known as microbial surface components recognizing adhesive matrix molecules (MSCRAMMs). Here, we focus on one of them, the clumping factor A (ClfA), which has been found to bind Fg through the dock-lock-latch mechanism. Interestingly, it has recently been discovered that MSCRAMM proteins employ a catch-bond to withstand forces exceeding 2 nN, making this type of interaction as mechanically strong as a covalent bond. However, it is not known whether this strength is an evolved feature characteristic of the bacterial protein or is typical only of the interaction with its partner. Here, we combine single-molecule force spectroscopy, biophysical binding assays, and molecular simulations to study the intrinsic mechanical strength of ClfA. We find that despite the extremely high forces required to break its interactions with Fg, ClfA is not by itself particularly strong. Integrating the results from both theory and experiments we dissect contributions to the mechanical stability of this protein.
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Coagulasa , Fibrinógeno , Staphylococcus aureus , Staphylococcus aureus/metabolismo , Staphylococcus aureus/química , Coagulasa/metabolismo , Coagulasa/química , Fibrinógeno/química , Fibrinógeno/metabolismo , Unión Proteica , Adhesinas Bacterianas/metabolismo , Adhesinas Bacterianas/química , Humanos , Estabilidad ProteicaRESUMEN
Pet food have been considered as possible vehicles of bacterial pathogens. The sudden boom of the pet food industry due to the worldwide increase in companion animal ownership calls for pet food investigations. Herein, this study aimed to determine the frequency, antimicrobial susceptibility profile, and molecular characteristics of coagulase-negative staphylococci (CoNS) in different pet food brands in Brazil. Eighty-six pet food packages were screened for CoNS. All isolates were identified at species level by MALDI-TOF MS and species-specific PCR. Antimicrobial susceptibility testing was performed by disc diffusion and broth microdilution (vancomycin and teicoplanin only) methods. The D-test was used to screen for inducible clindamycin phenotype (MLS-B). SCCmec typing and detection of mecA, vanA, vanB, and virulence-encoding genes were done by PCR. A total of 16 (18.6 %) CoNS isolates were recovered from pet food samples. Isolates were generally multidrug-resistant (MDR). All isolates were completely resistant (100 %) to penicillin. Resistances (12.5 % - 75 %) were also observed for fluoroquinolones, sulfamethoxazole-trimethoprim, tetracycline, rifampicin, erythromycin, and tobramycin. Isolates were susceptible to vancomycin (MICs <0.25-1 µg/mL) and teicoplanin (MICs <0.25-4 µg/mL). Intriguingly, 3/8 (37.5 %) CoNS isolates with the ERYRCLIS antibiotype expressed MLS-B phenotype. All isolates harboured blaZ gene. Seven (43.8 %) isolates carried mecA; and among them, the SCCmec Type III was the most frequent (n = 5/7; 71.4 %). Isolates also harboured seb, see, seg, sej, sem, etb, tsst, pvl, and hla toxin virulence-encoding genes (6.3 % - 25 %). A total of 12/16 (75 %) isolates were biofilm producers, while the icaAB gene was detected in an S. pasteuri isolate. Herein, it is shown that pet food is a potential source of clinically important Gram-positive bacterial pathogens. To the best of our knowledge, this is the first report of MLS-B phenotype and MR-CoNS in pet food in Latin America.
Asunto(s)
Antibacterianos , Clindamicina , Coagulasa , Pruebas de Sensibilidad Microbiana , Staphylococcus , Staphylococcus/efectos de los fármacos , Staphylococcus/genética , Staphylococcus/aislamiento & purificación , Brasil , Antibacterianos/farmacología , Coagulasa/metabolismo , Animales , Clindamicina/farmacología , Meticilina/farmacología , Alimentación Animal/microbiología , Microbiología de Alimentos , Mascotas/microbiología , Farmacorresistencia Bacteriana Múltiple/genéticaRESUMEN
Coagulase-negative Staphylococcus (CoNS) species inhibiting Staphylococcus aureus has been described in the skin of atopic dermatitis (AD) patients. This study evaluated whether Staphylococcus spp. from the skin and nares of AD and non-AD children produced antimicrobial substances (AMS). AMS production was screened by an overlay method and tested against NaOH, proteases and 30 indicator strains. Clonality was assessed by pulsed-field gel electrophoresis. Proteinaceous AMS-producers were investigated for autoimmunity by the overlay method and presence of bacteriocin genes by polymerase chain reaction. Two AMS-producers had their genome screened for AMS genes. A methicillin-resistant S. aureus (MRSA) produced proteinaceous AMS that inhibited 51.7% of the staphylococcal indicator strains, and it was active against 60% of the colonies selected from the AD child where it was isolated. On the other hand, 57 (8.8%) CoNS from the nares and skin of AD and non-AD children, most of them S. epidermidis (45.6%), reduced the growth of S. aureus and other CoNS species. Bacteriocin-related genes were detected in the genomes of AMS-producers. AMS production by CoNS inhibited S. aureus and other skin microbiota species from children with AD. Furthermore, an MRSA colonizing a child with AD produced AMS, reinforcing its contribution to dysbiosis and disease severity.
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Coagulasa , Dermatitis Atópica , Staphylococcus aureus Resistente a Meticilina , Microbiota , Piel , Staphylococcus , Dermatitis Atópica/microbiología , Humanos , Staphylococcus aureus Resistente a Meticilina/genética , Piel/microbiología , Niño , Coagulasa/genética , Coagulasa/metabolismo , Staphylococcus/genética , Bacteriocinas/genética , Antibacterianos/farmacología , Preescolar , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: Recently, linezolid-resistant staphylococci have become an emerging problem worldwide. Understanding the mechanisms of resistance, molecular epidemiology and transmission of linezolid-resistant CoNS in hospitals is very important. METHODS: The antimicrobial susceptibilities of all isolates were determined by the microdilution method. The resistance mechanisms and molecular characteristics of the strains were determined using whole-genome sequencing and PCR. RESULTS: All the strains were resistant to oxacillin and carried the mecA gene; 13 patients (36.1%) had prior linezolid exposure. Most S. epidermidis and S. hominis isolates were ST22 and ST1, respectively. MLST typing and evolutionary analysis indicated most linezolid-resistant CoNS strains were genetically related. In this study, we revealed that distinct CoNS strains have different mechanisms of linezolid resistance. Among ST22-type S. epidermidis, acquisition of the T2504A and C2534T mutations in the V domain of the 23 S rRNA gene, as well as mutations in the ribosomal proteins L3 (L101V, G152D, and D159Y) and L4 (N158S), were linked to the development of linezolid resistance. In S. cohnii isolates, cfr, S158Y and D159Y mutations in the ribosomal protein L3 were detected. Additionally, emergence of the G2576T mutation and the cfr gene were major causes of linezolid resistance in S. hominis isolates. The cfr gene, G2576T and C2104T mutations, M156T change in L3 protein, and I188S change in L4 protein were found in S. capitis isolates. CONCLUSION: The emergence of linezolid-resistant CoNS in the environment is concerning because it involves clonal dissemination and frequently coexists with various drug resistance mechanisms.
Asunto(s)
Antibacterianos , Linezolid , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas , Centros de Atención Terciaria , Linezolid/farmacología , Humanos , China/epidemiología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/epidemiología , Antibacterianos/farmacología , Femenino , Masculino , Persona de Mediana Edad , Tipificación de Secuencias Multilocus , Anciano , Secuenciación Completa del Genoma , Staphylococcus/efectos de los fármacos , Staphylococcus/genética , Staphylococcus/clasificación , Staphylococcus/enzimología , Coagulasa/metabolismo , Coagulasa/genética , ARN Ribosómico 23S/genética , Adulto , Resistencia a la Meticilina/genética , Mutación , Proteínas Bacterianas/genéticaRESUMEN
Milk is a source of essential nutrients, but food safety across the milk supply chain has emerged as an integral part of food trade. Of the several food safety hazards, antimicrobial-resistant Staphylococcus species have emerged as one of the major microbial hazards with significant public health concerns. The present crosssectional study was undertaken with the objective to isolate Staphylococcus species from the milk supply chain, characterize isolates for antimicrobial resistance, and trace the origin of isolates using molecular techniques. Samples collected from the formal and informal milk supply chains showed prevalence of Staphylococcus species of 4.3% (n=720); isolates were identified as coagulase-positive (S. aureus 67.7% and S. intermedius 6.4%) and coagulase-negative (S. lentus 9.6%, S. sciuri 3.2%, S. xylosus 3.2%, S. schleiferi 3.2%, S. felis 3.2%, and S. gallinarum 3.2%) species. Staphylococcus isolates showed antimicrobial resistance to methicillin (32.2%), ß-lactam (41.9%), and macrolide-lincosamide-streptogramin B (3.2%). Staphylococcus isolates phenotypically resistant to methicillin also carried the mecA gene and displayed diverse pulsed field gel electrophoresis (PFGE) profiles, indicating their diverse origins in the milk supply chain. Based on the similarity of PFGE profile, the origin of one of the Staphylococcus isolates was traced to the soil in contact with milch cows. The findings of this study highlight the need for more comprehensive microbial risk analysis studies across the milk supply chain, capacity building, creation of awareness among stakeholders about the judicious use of antimicrobials, and protection of public health using a One-Health approach.
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Antibacterianos , Leche , Staphylococcus , Leche/microbiología , Animales , Staphylococcus/efectos de los fármacos , Staphylococcus/genética , Staphylococcus/aislamiento & purificación , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/epidemiología , Microbiología de Alimentos , Humanos , Bovinos , Proteínas Bacterianas/genética , Coagulasa/genética , Coagulasa/metabolismo , Farmacorresistencia Bacteriana/genéticaRESUMEN
BACKGROUND: Coagulase Negative Staphylococci have been widely associated with medical device implant treatment and immune-compromised patients. Despite having increasing interest in Coagulase Negative Staphylococci, few studies from Nepal have reported the association of these organisms with urinary tract infections, conjunctivitis, high vaginal swabs, and cerebrospinal fluid. This study was carried out to determine antibiotic susceptibility pattern and biofilm production among Coagulase Negative Staphylococci isolated from clinical samples at tertiary care hospital. METHODS: This study was a hospital based cross-sectional study in which 3690 clinical samples were included. Isolation and identification of isolates was done following standard microbiological protocol. Coagulase Negative Staphylococci were identified phenotypically on the basis of gram staining, slide and tube coagulase test and by various sugar fermentation tests. Antibiotic susceptibility test was done following Kirby Bauer disk diffusion method (Clinical and Laboratory Standards Institute 2020). Biofilm production was determined by Tissue Culture Plate technique. RESULTS: A total of 113 isolates of Coagulase Negative Staphylococci were detected. Among them S. epidermidis (45.1%), S. saprophyticus (23.9%), S. haemolyticus (16.8%), S. hominis (5.3%), S. capitis (2.7%), -----S. cohini (1.8%), S. lugdunensis (1.8%) and S. sciuri (2.7%) were identified phenotypically. All isolates were found to be resistant against Ampicillin and 111 (98.2%) were sensitive against Linezolid.23.9% of CoNS were strong biofilm producers, 19.5% moderate and 56.6 % were non/weak biofilm producers. CONCLUSIONS: It requires susceptibility test for prescribing antibiotics against Coagulase Negative Staphylococci in hospital and the misuse of antibiotics should be prevented.
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Coagulasa , Staphylococcus , Femenino , Humanos , Estudios Transversales , Centros de Atención Terciaria , Nepal , Antibacterianos/farmacología , BiopelículasRESUMEN
The human skin microbiome comprises diverse populations that differ temporally between body sites and individuals. The virome is a less studied component of the skin microbiome and the study of bacteriophages is required to increase knowledge of the modulation and stability of bacterial communities. Staphylococcus species are among the most abundant colonisers of skin and are associated with both health and disease yet the bacteriophages infecting the most abundant species on skin are less well studied. Here, we report the isolation and genome sequencing of 40 bacteriophages from human skin swabs that infect coagulase-negative Staphylococcus (CoNS) species, which extends our knowledge of phage diversity. Six genetic clusters of phages were identified with two clusters representing novel phages, one of which we characterise and name Alsa phage. We identified that Alsa phages have a greater ability to infect the species S. hominis that was otherwise infected less than other CoNS species by the isolated phages, indicating an undescribed barrier to phage infection that could be in part due to numerous restriction-modification systems. The extended diversity of Staphylococcus phages here enables further research to define their contribution to skin microbiome research and the mechanisms that limit phage infection.
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Bacteriófagos , Humanos , Bacteriófagos/genética , Coagulasa/genética , Genoma Viral , Piel/microbiología , Fagos de Staphylococcus/genética , Staphylococcus/genéticaRESUMEN
BACKGROUND: In Ethiopia, milk production and handling practices often lack proper hygiene measures, leading to the potential contamination of milk and milk products with Staphylococcus aureus (S. aureus), including methicillin-resistant strains, posing significant public health concerns. This study aimed to investigate the occurrence, antimicrobial susceptibility profiles and presence of resistance genes in S. aureus strains isolated from milk and milk products. METHODS: A cross-sectional study was conducted in the Arsi highlands, Oromia, Ethiopia from March 2022 to February 2023. A total of 503 milk and milk product samples were collected, comprising 259 raw milk, 219 cottage cheese, and 25 traditional yogurt samples. S. aureus isolation and coagulase-positive staphylococci enumeration were performed using Baird-Parker agar supplemented with tellurite and egg yolk. S. aureus was further characterized based on colony morphology, Gram stain, mannitol fermentation, catalase test, and coagulase test. Phenotypic antimicrobial resistance was assessed using the Kirby-Bauer disc diffusion method, while the polymerase chain reaction (PCR) was employed for confirming the presence of S. aureus and detecting antimicrobial resistance genes. RESULTS: S. aureus was detected in 24.9% of the milk and milk products, with the highest occurrence in raw milk (40.9%), followed by yogurt (20%), and cottage cheese (6.4%). The geometric mean for coagulase-positive staphylococci counts in raw milk, yogurt, and cottage cheese was 4.6, 3.8, and 3.2 log10 CFU/mL, respectively. Antimicrobial resistance analysis revealed high levels of resistance to ampicillin (89.7%) and penicillin G (87.2%), with 71.8% of the isolates demonstrating multidrug resistance. Of the 16 S. aureus isolates analyzed using PCR, all were found to carry the nuc gene, with the mecA and blaZ genes detected in 50% of these isolates each. CONCLUSION: This study revealed the widespread distribution of S. aureus in milk and milk products in the Arsi highlands of Ethiopia. The isolates displayed high resistance to ampicillin and penicillin, with a concerning level of multidrug resistance. The detection of the mecA and blaZ genes in selected isolates is of particular concern, highlighting a potential public health hazard and posing a challenge to effective antimicrobial treatment. These findings highlight the urgent need to enhance hygiene standards in milk and milk product handling and promote the rational use of antimicrobial drugs. Provision of adequate training for all individuals involved in the dairy sector can help minimize contamination. These measures are crucial in addressing the threats posed by S. aureus, including methicillin-resistant strains, and ensuring the safety of milk and its products for consumers.
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Antiinfecciosos , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Animales , Staphylococcus aureus , Leche , Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/genética , Coagulasa/genética , Etiopía , Estudios Transversales , Infecciones Estafilocócicas/epidemiología , Staphylococcus , Antiinfecciosos/farmacología , Ampicilina/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: Inevitably, the floors of mosques are contaminated with microorganisms, and the risk of pathogen transmission is probably high between the many visitors, but the issue has been infrequently studied. OBJECTIVES: Investigate microorganism variety and risk of contamination on commonly used carpets and rosaries (prayer beads). DESIGN: Cross-sectional. SETTINGS: Mosques. METHODS: This study was carried out in three different cities of Turkey in 2023, focusing on mosques located around hospitals. Forty mosques were included in the study and from each mosque 10 samples were collected from various parts of carpets and rosaries. The number of positive culture isolates were identified. MAIN OUTCOME MEASURES: Diversity and distribution of microorganisms isolated from mosque carpets and rosaries; methicillin-resistance rates in Staphylococci. SAMPLE SIZE: 400 samples. RESULTS: Growth was observed in 368 (92%) of 400 samples examined. The microorganisms isolated in the highest number were methicillin-susceptible coagulase negative Staphylococci (MSCoNS) (59.8%), Microcooccus (41%) and diphtheroids (31.3%). The rates of total growth (P=.001), including diphtheroids (P=.018), methicillin-resistant coagulase negative Staphylococci (P=.001), Bacillus spp. (P=.036) and Aspergillus spp. (P=.002) rates were significantly higher in the rosary samples than carpet samples. At mosques in Tokat, a province center, 4 samples were positive for Acinetobacter baumannii, two samples were positive for Pseudomonas aeruginosa and one sample for methicillin-resistant Staphylococcus aureus (MRSA), and these were isolated from rosaries. 0.3% of Staphylococcus isolates were MRSA. CONCLUSION: As there is a high risk of contamination of carpets and prayer beads on the mosque floor with human flora, the use of appropriate hygiene practices is necessary. We also found some emerging bacteria in addition to the normal human flora. LIMITATIONS: Our study was conducted in three provinces. Further studies might cover a wider geography.
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Coagulasa , Staphylococcus aureus Resistente a Meticilina , Humanos , Estudios Transversales , Pisos y Cubiertas de Piso , MeticilinaRESUMEN
This study was condcuted to examine the association of area under the curve (AUC)/minimum inhibitory concentration (MIC) and trough concentration (Ctrough) of vancomycin with treatment outcome and nephrotoxicity in infections caused by Enterococcus spp. and coagulase-negative Staphylococci (CoNS). Peak and trough concentrations were used to calculate AUC in 89 patients receiving vancomycin for infections with Enterococcus spp. (n = 65) or CoNS (n = 24). Correlations between Ctrough, AUC/MIC, early clinical response (ECR), and nephrotoxicity were assessed and cutoff values were determined. Sixty-three (70.8%) patients showed improvement in ECR and 10 (11.2%) experienced nephrotoxicity. Enterococcus spp. infections displayed correlations between AUC/MIC and ECR for AUC0-24 h/MIC (r2 = 0.27, P ≤ .05) and AUC24-48 h/MIC (r2 = 0.28, P ≤ .05), but not for Ctrough (r2 = 0.21, P > .05). There were no correlations between Ctrough (r2 = 0.26, P > .05), AUC0-24 h/MIC (r2 = -0.12, P > .05), AUC24-48 h/MIC (r2 = 0.01, P > .05) and ECR for CoNS. In the CoNS group, a moderate correlation was found between ECR and Ctrough at a cutoff value of 6.9 µg/mL. In addition, nephrotoxicity is also moderately associated with AUC0-24 h and AUC24-48 h at 505.7 and 667.1 µgâ¢h/mL, respectively. A strong correlation between nephrotoxicity and Ctrough was observed when the cutoff value was 18.9 µg/mL. AUC/MIC during the first 48 h was a determinant of vancomycin efficacy in Enterococcus infections but not for CoNS. Ctrough was not correlated with clinical outcome. Nephrotoxicity could be predicted using Ctrough and AUC for infections with both pathogens.
Asunto(s)
Antibacterianos , Área Bajo la Curva , Enterococcus , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas , Staphylococcus , Vancomicina , Humanos , Masculino , Femenino , Vancomicina/farmacocinética , Vancomicina/efectos adversos , Vancomicina/sangre , Vancomicina/administración & dosificación , Vancomicina/uso terapéutico , Antibacterianos/farmacocinética , Antibacterianos/efectos adversos , Antibacterianos/administración & dosificación , Antibacterianos/sangre , Antibacterianos/uso terapéutico , Persona de Mediana Edad , Staphylococcus/efectos de los fármacos , Estudios Prospectivos , Anciano , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Enterococcus/efectos de los fármacos , Adulto , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Coagulasa/metabolismo , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
First generation cephalosporins such cephalothin of cefazolin are indicated for antimicrobial prophylaxis for clean and clean contaminated surgical procedures because its antimicrobial spectrum, relative low toxicity and cost. Anesthesia and surgery could alter the pharmacokinetic behavior of different drugs administered perioperative by many mechanisms that affect distribution, metabolism or excretion processes. Intravenous administration of the antimicrobial within 30 and 60 min before incision is recommended in order to reach therapeutic serum and tissue concentrations and redosing is recommended if the duration of the procedure exceeds two half-life of the antimicrobial. To the author's knowledge there are no pharmacokinetic studies of cephalothin in dogs under anesthesia/surgery conditions. The aim of this study was (1) to evaluate the pharmacokinetics of cephalothin in anesthetized dogs undergoing ovariohysterectomy by a nonlinear mixed-effects model and to determine the effect of anesthesia/surgery and other individual covariates on its pharmacokinetic behavior; (2) to determine the MIC and conduct a pharmacodynamic modeling of time kill curves assay of cephalothin against isolates of Staphylococcus spp. isolated from the skin of dogs; (3) to conduct a PK/PD analysis by integration of the obtained nonlinear mixed-effects models in order to evaluate the antimicrobial effect of changing concentrations on simulated bacterial count; and (4) to determine the PK/PD endpoints and PK/PDco values in order to predict the optimal dose regimen of cephalothin for antimicrobial prophylaxis in dogs. Anesthesia/surgery significantly reduced cephalothin clearance by 18.78%. Based on the results of this study, a cephalothin dose regimen of 25 mg/kg q6h by intravenous administration showed to be effective against Staphylococcus spp. isolates with MIC values ≤2 µg/mL and could be recommended for antimicrobial prophylaxis for clean surgery in healthy dogs.
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Enfermedades de los Perros , Infecciones Estafilocócicas , Perros , Animales , Cefalotina/farmacología , Cefalotina/uso terapéutico , Antibacterianos , Staphylococcus aureus , Coagulasa/farmacología , Coagulasa/uso terapéutico , Infecciones Estafilocócicas/prevención & control , Infecciones Estafilocócicas/veterinaria , Staphylococcus , Pruebas de Sensibilidad Microbiana/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/prevención & controlRESUMEN
BACKGROUND: Infective endocarditis continues to be a significant concern and may be undergoing an epidemiological transition. METHODS: Were studied 1804 consecutive episodes of infective endocarditis between 1978 and 2022. The mean age was 48 ( ± 19), and 1162 (64%) patients were male. Temporal trends in demographic data, comorbidities, predisposing conditions, microorganisms, complications and in-hospital death have been studied over the decades (1978-1988, 1989-1999, 2000-2010 and 2011-2022). The outcomes and clinical characteristics were modeled using nonlinear cubic spline functions. FINDINGS: Valve surgery was performed in 50% of the patients and overall in-hospital mortality was 30%. From the first to the fourth decade studied, the average age of patients increased from 29 to 57 years (p < 0.001), with significant declines in the occurrence of rheumatic valvular heart disease (15% to 6%; p < 0.001) and streptococcal infections (46% to 33%; p < 0.001). Healthcare-associated infections have increased (9% to 21%; p < 0.001), as have prosthetic valve endocarditis (26% to 53%; p < 0.001), coagulase-negative staphylococcal infections (4% to 11%; p < 0.001), and related-complications (heart failure, embolic events, and perivalvular abscess; p < 0.001). These changes were associated with a decline in adjusted in-hospital mortality from 34% to 25% (p = 0.019). INTERPRETATION: In the 44 years studied, there was an increase in the mean age of patients, healthcare-related, prosthetic valve, coagulase-negative staphylococci/MRSA infections, and related complications. Notably, these epidemiological changes were associated with a decline in the adjusted in-hospital mortality.
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Endocarditis Bacteriana , Endocarditis , Prótesis Valvulares Cardíacas , Infecciones Relacionadas con Prótesis , Infecciones Estafilocócicas , Humanos , Masculino , Adulto , Persona de Mediana Edad , Femenino , Endocarditis Bacteriana/cirugía , Mortalidad Hospitalaria , Coagulasa , Prótesis Valvulares Cardíacas/efectos adversos , Infecciones Relacionadas con Prótesis/epidemiología , Endocarditis/epidemiología , Staphylococcus , Infecciones Estafilocócicas/complicacionesRESUMEN
The species- and clone-specific susceptibility of Staphylococcus cells for bacteriophages is governed by the structures and glycosylation patterns of wall teichoic acid (WTA) glycopolymers. The glycosylation-dependent phage-WTA interactions in the opportunistic pathogen Staphylococcus epidermidis and in other coagulase-negative staphylococci (CoNS) have remained unknown. We report a new S. epidermidis WTA glycosyltransferase TagE whose deletion confers resistance to siphoviruses such as ΦE72 but enables binding of otherwise unbound podoviruses. S. epidermidis glycerolphosphate WTA was found to be modified with glucose in a tagE-dependent manner. TagE is encoded together with the enzymes PgcA and GtaB providing uridine diphosphate-activated glucose. ΦE72 transduced several other CoNS species encoding TagE homologs, suggesting that WTA glycosylation via TagE is a frequent trait among CoNS that permits interspecies horizontal gene transfer. Our study unravels a crucial mechanism of phage-Staphylococcus interaction and horizontal gene transfer, and it will help in the design of anti-staphylococcal phage therapies.IMPORTANCEPhages are highly specific for certain bacterial hosts, and some can transduce DNA even across species boundaries. How phages recognize cognate host cells remains incompletely understood. Phages infecting members of the genus Staphylococcus bind to wall teichoic acid (WTA) glycopolymers with highly variable structures and glycosylation patterns. How WTA is glycosylated in the opportunistic pathogen Staphylococcus epidermidis and in other coagulase-negative staphylococci (CoNS) species has remained unknown. We describe that S. epidermidis glycosylates its WTA backbone with glucose, and we identify a cluster of three genes responsible for glucose activation and transfer to WTA. Their inactivation strongly alters phage susceptibility patterns, yielding resistance to siphoviruses but susceptibility to podoviruses. Many different CoNS species with related glycosylation genes can exchange DNA via siphovirus ΦE72, suggesting that glucose-modified WTA is crucial for interspecies horizontal gene transfer. Our finding will help to develop antibacterial phage therapies and unravel routes of genetic exchange.
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Infecciones Estafilocócicas , Staphylococcus epidermidis , Humanos , Staphylococcus epidermidis/genética , Staphylococcus epidermidis/metabolismo , Staphylococcus aureus/genética , Coagulasa/metabolismo , Glucosa/metabolismo , Ácidos Teicoicos/metabolismo , Staphylococcus/metabolismo , Fagos de Staphylococcus/genética , ADN/metabolismo , Pared Celular/metabolismo , Infecciones Estafilocócicas/metabolismoRESUMEN
To investigate the incidence, risk factors, and pathogenic characteristics of catheter-related bloodstream infection caused by peripherally inserted central venous catheter in neonates, and to provide references for reducing the infection rate of peripherally inserted central venous catheter. The clinical data of 680 neonates who underwent peripherally inserted central catheter (PICC) in the neonatal intensive care unit from June 2020 to June 2023 were retrospectively analyzed. The risk factors and independent risk factors of catheter-related bloodstream infection caused by PICC were determined by univariate and multivariate analysis, respectively. Catheter-related bloodstream infection occurred in 38 of 680 neonates who underwent PICC. The infection rate was 4.74%. The proportions of fungi, gram-positive bacteria, and gram-negative bacteria were 42.11%, 36.84%, and 21.05%, respectively. Candida parapsilosis was the main fungus (18.42%), coagulase negative Staphylococcus was the main gram-positive bacteria (23.68%), and Klebsiella pneumoniae and Escherichia coli were the main gram-negative bacteria (7.89%). Univariate analysis showed that gestational age ≤32 weeks, birth weight ≤1500 g, congenital diseases, nutritional support, catheterization time, 5-minute APGAR score ≤7, and neonatal respiratory distress syndrome were associated with catheter-related bloodstream infection caused by PICC. Multivariate analysis showed that premature delivery, low birth weight, parenteral nutrition, long catheterization time, and 5-minute APGAR score ≤7 were associated with catheter-related bloodstream infection caused by PICC. Among the pathogens detected, there were 6 cases of K pneumoniae, 5 cases of coagulase negative staphylococci, and 2 cases of fungi. Low birth weight, premature delivery, off-site nutrition, long catheterization time, and 5-minute APGAR score ≤7 are independent risk factors for catheter-related bloodstream infection in neonates with peripherally inserted central venous catheters. The pathogenic bacteria are fungi and multidrug-resistant bacteria.
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Infecciones Relacionadas con Catéteres , Cateterismo Venoso Central , Cateterismo Periférico , Catéteres Venosos Centrales , Sepsis , Recién Nacido , Humanos , Lactante , Estudios Retrospectivos , Coagulasa , Infecciones Relacionadas con Catéteres/microbiología , Sepsis/etiología , Cateterismo Periférico/efectos adversos , Factores de Riesgo , Cateterismo Venoso Central/efectos adversosRESUMEN
Since September 2018, serious meningitis has been found on some breeding-duck farms in Shandong Province, China. A large number of ducks exhibit severe neurological symptoms. The ducks were randomly selected for laboratory testing. Duck brain samples were collected using standard sterile techniques, and the staphylococci isolates were detected in 404 (70.14%) out of 576 brain samples. A total of 525 coagulase-negative staphylococci (CoNS) strains were isolated, including 6 species: Staphylococcus sciuri (S. sciuri) (67.24%, 353/525), Staphylococcus epidermidis (S. epidermidis) (9.71%, 51/525), Staphylococcus saprophyticus (S. saprophyticus) (8.38%, 44/525), Staphylococcus lentus (S. lentus) (7.62%, 40/525), Staphylococcus haemolyticus (S. haemolyticus) (2.48%, 13/525), and Staphylococcus xylosus (S. xylosus) (4.57%, 24/525). Mixed strain infections were detected in 121 (29.95%) infected presentations. The antimicrobial susceptibility testing indicated that 40.38% of the isolates exhibited multi-drug resistance, and 53.90% of the strains were methicillin-resistant strains by amplification of the methicillin resistance gene (mecA) gene. Through experimental reproduction of the disease, we determined that the CoNS strains were the leading pathogens causing bacterial meningitis in ducks. Although these CoNS strains does not directly cause the death of sick ducks, they still cause large economic losses due to the retarded growth and development of the sick ducks, lower feed returns, and lower grades of processed duck products. The results of this study will contribute to our understanding of the epidemiology and pathogenesis of CoNS and be helpful in the prevention and treatment of the infection.
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Coagulasa , Patos , Meningitis Bacterianas , Enfermedades de las Aves de Corral , Infecciones Estafilocócicas , Staphylococcus , Animales , Staphylococcus/efectos de los fármacos , Staphylococcus/aislamiento & purificación , Staphylococcus/enzimología , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/epidemiología , Infecciones Estafilocócicas/veterinaria , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/epidemiología , Coagulasa/metabolismo , Meningitis Bacterianas/veterinaria , Meningitis Bacterianas/microbiología , Meningitis Bacterianas/epidemiología , China/epidemiología , Antibacterianos/farmacologíaRESUMEN
PURPOSE: Coagulase-negative staphylococci (CoNS) are Gram-positive organisms that are a known component of normal skin flora and the most common cause of nosocomial bacteremia. For CoNS species, the vancomycin MIC breakpoint for susceptibility set by the Clinical and Laboratory Standards Institute is ≤4 µg/mL. There has been published reports of vancomycin heteroresistance in CoNS with vancomycin MICs of 2 to 4 µg/mL. The aim of this retrospective cohort analysis was to assess the clinical impact of vancomycin MICs <2 µg/mL versus ≥2 µg/mL in adult patients with CoNS bloodstream infections. METHODS: Adult patients admitted to University Medical Center New Orleans with a blood culture positive for CoNS were assessed. The primary outcome was difference in 30-day mortality. Secondary outcomes were in-hospital, all-cause mortality; duration of bacteremia; hospital length of stay; and percentage of oxacillin-resistant CoNS. FINDINGS: There was no difference in mortality in the vancomycin MIC <2 µg/mL group versus the vancomycin MIC ≥2 µg/mL group at 30 days (15.4% vs 17.4%; P = 1). In-hospital, all-cause mortality was also not different between groups (11.5% vs 13%; P = 1). Hospital length of stay between groups was 28.2 days versus 21 days (P = 0.692). Median duration of bacteremia was 1 day in both groups (P = 0.975), and median scheduled duration of antibiotic therapy was 14.9 days and 19.5 days (P = 0.385). The source and mode of acquisition of CoNS were similar between groups. Of all CoNS isolates, 58.7% (44 of 75) were oxacillin resistant. Staphylococcus epidermidis was the most common CoNS species at 66.7% (50 of 75). Of all isolates, 30.7% (23 of 75) had a vancomycin MIC ≥2 µg/mL, and 87% (20 of 23) of these were S. epidermidis. There was a higher percentage of S. epidermidis in the vancomycin MIC ≥2 µg/mL group than in the MIC <2 µg/mL group (87% vs 57.7%; P = 0.012). CoNS with a vancomycin MIC ≥2 µg/mL were also more likely to be oxacillin resistant (78.3% vs 50%; P = 0.005). IMPLICATIONS: There was no difference in clinical outcomes in adult patients with a CoNS bloodstream infection with a vancomycin MIC <2 µg/mL versus ≥2 µg/mL. At present, vancomycin remains appropriate empiric therapy for CoNS bloodstream infection. Further research is needed to determine if there is a true clinical impact of a vancomycin MIC ≥2 µg/mL in CoNS infections.
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Antibacterianos , Bacteriemia , Coagulasa , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas , Staphylococcus , Vancomicina , Humanos , Vancomicina/uso terapéutico , Vancomicina/farmacología , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Bacteriemia/mortalidad , Masculino , Estudios Retrospectivos , Femenino , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Coagulasa/metabolismo , Staphylococcus/efectos de los fármacos , Staphylococcus/aislamiento & purificación , Anciano , Resultado del Tratamiento , Adulto , Tiempo de Internación/estadística & datos numéricosRESUMEN
Coagulase-negative staphylococci (CoNS) are a group of gram-positive staphylococcal species that naturally inhabit the healthy human skin and mucosa. The clinical impact of CoNS-associated infections has recently been regarded as a challenge for diagnosis and therapeutic options. CoNS-associated infections are primarily caused by bacterial resistance to antibiotics and biofilm formation. As antibiotics are still the most used treatment, this problem will likely persist in the future. The present study aimed to investigate the resistance and virulence of CoNS recovered from various acne lesions and explore their genetic basis. Skin swab samples were collected from participants with acne and healthy skin. All samples underwent conventional culture for the isolation of CoNS, MALDI-TOF confirmation, antibiotic susceptibility, and biofilm formation testing. A total of 85 CoNS isolates were recovered from the samples and preliminarily identified as Staphylococcus epidermidis. Isolates from the acne group (n = 60) showed the highest rates of resistance to penicillin (73%), cefoxitin (63%), clindamycin (53.3%), and erythromycin (48%), followed by levofloxacin (36.7%) and gentamycin (31.7%). The lowest rates of resistance were observed against tetracycline (28.3%), doxycycline (11.7%), and minocycline (8.3%). CoNS isolated from mild, moderate acne and healthy isolates did not show strong biofilm formation, whereas the isolates from the severe cases of the acne group showed strong biofilm formation (76.6%). Four extensively drug-resistant and strong biofilm-forming staphylococcal isolates recovered from patients with severe acne were selected for whole-genome sequencing (WGS), and their genomes were investigated using bioinformatics tools. Three of the sequenced genomes were identified as S. epidermidis; however, isolate 29AM was identified as Staphylococcus warneri, which is a newly emerging pathogen that is not commonly associated with acne and was not detected by MALDI-TOF. All the sequenced strains were multidrug-resistant and carried multiple resistance genes, including blaZ, mecA, tet(K), erm(C), lnuA, vgaA, dfrC, fusB, fosBx1, norA, and vanT, which were found to be located on plasmids and chromosomes. Virulence features were detected in all genomes in the presence of genes involved in adherence and biofilm formation (icaA, icaB, icaC, sdrG, sdrH, atl, ebh, and ebp). Only the S. warneri isolate 29AM contained immune evasion genes (capB, capC, acpXL, and manA), an anti-phagocytosis gene (cdsA), and other unique features. As a result of their potential pathogenicity and antibiotic resistance, CoNS must be monitored as an emerging pathogen associated with acne infections. To the best of our knowledge, this is the first report to isolate, identify, and correlate S. warneri with severe acne infections among Egyptian patients using WGS and bioinformatic analysis.
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Acné Vulgar , Infecciones Estafilocócicas , Humanos , Coagulasa/genética , Egipto , Infecciones Estafilocócicas/microbiología , Staphylococcus , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Staphylococcus epidermidis/genética , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: Chronic bovine mastitis is linked to biofilm-producing Staphylococcus aureus (bp-Sa) or Staphylococcus coagulase-negative (bp-Scn). OBJECTIVES: Bp-Sa and bp-Scn were treated with intramammary preparations of either enrofloxacin HCl·2H2O-dimethyl-sulfoxide-chitosan (enro-C/DMSO/chitosan) or enro-C alone. Their potential to inhibit and degrade biofilm formation in vitro was also assessed. METHODS: Milk samples were obtained from the affected quarters in a herd. Phenotypical and genotypical identifications as biofilm-producing Staphylococcus species were carried out. Enro-C/DMSO/chitosan and enro-C alone were assessed to determine their in vitro efficacy in interfering with biofilm formation and their bactericidal effects. A prolonged eight-day treatment with a twice-daily intramammary insertion of 10 mL of enro-C/DMSO/chitosan or enro-C alone was set to evaluate the clinical and bacteriological cures on day 10 in 15 cows per group and the biofilm-inhibiting ability. RESULTS: Fifty-seven percent of the isolates were identified as Staphylococcus spp., of which 50% were bp-Sa, 46% bp-Scn, and 4% Staphylococcus pseudintermedius. One hundred percent of the S. aureus isolated and 77% of Staphylococcus coagulase-negative were biofilm producers. In both groups, the icaA and icaD biofilm-producing genes were identified. The experimental preparation could inhibit biofilm formation, degrade mature biofilms, and have well-defined microbicidal effects on planktonic and biofilm bacteria. The respective clinical and bacteriological cure rates were 100% and 80% for enro-C/DMSO/chitosan and 41.7% and 25% for enro-C alone. CONCLUSIONS: Enro-C/DMSO/chitosan eliminates bp-Sa and bp-Scn from cases of chronic bovine mastitis.