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1.
BMC Infect Dis ; 21(1): 526, 2021 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-34090384

RESUMEN

BACKGROUND: Klebsiella spp. are important pathogens associated with bacteremia among admitted children and is among the leading cause of death in children < 5 years in postmortem studies, supporting a larger role than previously considered in childhood mortality. Herein, we compared the antimicrobial susceptibility, mechanisms of resistance, and the virulence profile of Klebsiella spp. from admitted and postmortem children. METHODS: Antimicrobial susceptibility and virulence factors of Klebsiella spp. recovered from blood samples collected upon admission to the hospital (n = 88) and postmortem blood (n = 23) from children < 5 years were assessed by disk diffusion and multiplex PCR. RESULTS: Klebsiella isolates from postmortem blood were likely to be ceftriaxone resistant (69.6%, 16/23 vs. 48.9%, 43/88, p = 0.045) or extended-spectrum ß-lactamase (ESBL) producers (60.9%, 14/23 vs. 25%, 22/88, p = 0.001) compared to those from admitted children. blaCTX-M-15 was the most frequent ESBL gene: 65.3%, 9/14 in postmortem isolates and 22.7% (5/22) from admitted children. We found higher frequency of genes associated with hypermucoviscosity phenotype and invasin in postmortem isolates than those from admitted children: rmpA (30.4%; 7/23 vs. 9.1%, 8/88, p = 0.011), wzi-K1 (34.7%; 8/23 vs. 8%; 7/88, p = 0.002) and traT (60.8%; 14/23 vs. 10.2%; 9/88, p < 0.0001), respectively. Additionally, serine protease auto-transporters of Enterobacteriaceae were detected from 1.8% (pic) to 12.6% (pet) among all isolates. Klebsiella case fatality rate was 30.7% (23/75). CONCLUSION: Multidrug resistant Klebsiella spp. harboring genes associated with hypermucoviscosity phenotype has emerged in Mozambique causing invasive fatal disease in children; highlighting the urgent need for prompt diagnosis, appropriate treatment and effective preventive measures for infection control.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Infecciones por Enterobacteriaceae/mortalidad , Klebsiella/efectos de los fármacos , Klebsiella/genética , Factores de Virulencia/genética , Autopsia , Bacteriemia/epidemiología , Bacteriemia/microbiología , Preescolar , Infecciones por Enterobacteriaceae/microbiología , Femenino , Humanos , Lactante , Recién Nacido , Klebsiella/aislamiento & purificación , Masculino , Pruebas de Sensibilidad Microbiana , Mozambique/epidemiología , beta-Lactamasas/genética
2.
Nat Commun ; 12(1): 2684, 2021 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-33976138

RESUMEN

Shigella sonnei is the most common agent of shigellosis in high-income countries, and causes a significant disease burden in low- and middle-income countries. Antimicrobial resistance is increasingly common in all settings. Whole genome sequencing (WGS) is increasingly utilised for S. sonnei outbreak investigation and surveillance, but comparison of data between studies and labs is challenging. Here, we present a genomic framework and genotyping scheme for S. sonnei to efficiently identify genotype and resistance determinants from WGS data. The scheme is implemented in the software package Mykrobe and tested on thousands of genomes. Applying this approach to analyse >4,000 S. sonnei isolates sequenced in public health labs in three countries identified several common genotypes associated with increased rates of ciprofloxacin resistance and azithromycin resistance, confirming intercontinental spread of highly-resistant S. sonnei clones and demonstrating the genomic framework can facilitate monitoring the spread of resistant clones, including those that have recently emerged, at local and global scales.


Asunto(s)
Disentería Bacilar/diagnóstico , Genoma Bacteriano/genética , Genómica/métodos , Shigella sonnei/genética , Antibacterianos/farmacología , Australia , Azitromicina/farmacología , Ciprofloxacina/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Disentería Bacilar/microbiología , Inglaterra , Genética de Población , Genotipo , Geografía , Salud Global , Humanos , Pruebas de Sensibilidad Microbiana/métodos , Filogenia , Polimorfismo de Nucleótido Simple , Shigella sonnei/clasificación , Shigella sonnei/fisiología , Estados Unidos , Secuenciación Completa del Genoma
3.
Nat Commun ; 12(1): 2653, 2021 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-33976161

RESUMEN

Plasmid persistence in bacterial populations is strongly influenced by the fitness effects associated with plasmid carriage. However, plasmid fitness effects in wild-type bacterial hosts remain largely unexplored. In this study, we determined the fitness effects of the major antibiotic resistance plasmid pOXA-48_K8 in wild-type, ecologically compatible enterobacterial isolates from the human gut microbiota. Our results show that although pOXA-48_K8 produced an overall reduction in bacterial fitness, it produced small effects in most bacterial hosts, and even beneficial effects in several isolates. Moreover, genomic results showed a link between pOXA-48_K8 fitness effects and bacterial phylogeny, helping to explain plasmid epidemiology. Incorporating our fitness results into a simple population dynamics model revealed a new set of conditions for plasmid stability in bacterial communities, with plasmid persistence increasing with bacterial diversity and becoming less dependent on conjugation. These results help to explain the high prevalence of plasmids in the greatly diverse natural microbial communities.


Asunto(s)
Bacterias/genética , Transferencia de Gen Horizontal , Genes Bacterianos/genética , Variación Genética , Genoma Bacteriano/genética , Plásmidos/genética , Algoritmos , Antibacterianos/farmacología , Bacterias/clasificación , Farmacorresistencia Bacteriana Múltiple/genética , Enterobacteriaceae/clasificación , Enterobacteriaceae/genética , Microbioma Gastrointestinal/genética , Humanos , Microbiota/genética , Filogenia , Especificidad de la Especie
4.
Curr Microbiol ; 78(6): 2414-2419, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33961094

RESUMEN

The presence of multidrug-resistant Escherichia coli of fecal origin in seafood is a serious concern. Seafood containing MDR E. coli can serve as a medium for the transfer of resistant bacteria to consumers. The aim of the present study is to isolate and identify multidrug-resistant E. coli and associated resistant genes from selected seafood (catfish, crabs and tilapia fish) purchased from wholesalers and retailers at sea landing areas in Lagos state, Nigeria. A total of two hundred and thirty-eight (238) samples consisting of catfish (52), tilapia fish (78) and crab (108) were collected and investigated for the presence of E. coli from the period of June 2018-April 2019. Colonies that showed metallic sheen were considered presumptive E. coli isolates, and positive isolates were chosen for further confirmed by biochemical methods using IMViC tests, Oxidase test, triple sugar iron agar test and sugar fermentation test. Antimicrobial susceptibility of the isolates to eight classes of antibiotics was determined by disc diffusion methods while amplification of suspected antibiotic resistance genes were done by the polymerase chain reaction (PCR) using specific primers. A total of 105 (44.1%) E. coli were isolated from selected samples by standard microbiological procedures. The grand total of 59 (56.2%) isolates showed multiple antibiotic-resistant patterns. The overall result showed high-level resistance to tetracycline 101/105 (96.1%) and trimethoprim 90/105 (85.7%), cefotaxime 67/105 (42.9%) while the highest susceptibility of 101/105 (96.2%) was recorded for amikacin followed by gentamicin 84/105 (80%), meropenem 75/105 (71.4%), ceftazidime (69.5). The presence of tetA and blaTEM was prevalent among the isolates. Our results indicate that seafood may be a reservoir of ß-lactam and tetracycline-resistance determinants.


Asunto(s)
Bagres , Escherichia coli , Animales , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Escherichia coli/genética , Incidencia , Pruebas de Sensibilidad Microbiana , Nigeria , Alimentos Marinos
5.
Nat Commun ; 12(1): 2716, 2021 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-33976135

RESUMEN

Polyclonal infections occur when at least two unrelated strains of the same pathogen are detected in an individual. This has been linked to worse clinical outcomes in tuberculosis, as undetected strains with different antibiotic resistance profiles can lead to treatment failure. Here, we examine the amount of polyclonal infections in sputum and surgical resections from patients with tuberculosis in the country of Georgia. For this purpose, we sequence and analyse the genomes of Mycobacterium tuberculosis isolated from the samples, acquired through an observational clinical study (NCT02715271). Access to the lung enhanced the detection of multiple strains (40% of surgery cases) as opposed to just using a sputum sample (0-5% in the general population). We show that polyclonal infections often involve genetically distant strains and can be associated with reversion of the patient's drug susceptibility profile over time. In addition, we find different patterns of genetic diversity within lesions and across patients, including mutational signatures known to be associated with oxidative damage; this suggests that reactive oxygen species may be acting as a selective pressure in the granuloma environment. Our results support the idea that the magnitude of polyclonal infections in high-burden tuberculosis settings is underestimated when only testing sputum samples.


Asunto(s)
Farmacorresistencia Bacteriana Múltiple/genética , Genoma Bacteriano , Granuloma/patología , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/patología , Tuberculosis Pulmonar/patología , Antituberculosos/uso terapéutico , Biopsia , Células Clonales , Estudios de Cohortes , Variación Genética , Georgia (República) , Granuloma/tratamiento farmacológico , Granuloma/microbiología , Granuloma/cirugía , Humanos , Pulmón/microbiología , Pulmón/patología , Pulmón/cirugía , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/patogenicidad , Especies Reactivas de Oxígeno/metabolismo , Esputo/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/cirugía , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/cirugía
6.
Nat Commun ; 12(1): 2879, 2021 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-34001879

RESUMEN

As whole-genome sequencing capacity becomes increasingly decentralized, there is a growing opportunity for collaboration and the sharing of surveillance data within and between countries to inform typhoid control policies. This vision requires free, community-driven tools that facilitate access to genomic data for public health on a global scale. Here we present the Pathogenwatch scheme for Salmonella enterica serovar Typhi (S. Typhi), a web application enabling the rapid identification of genomic markers of antimicrobial resistance (AMR) and contextualization with public genomic data. We show that the clustering of S. Typhi genomes in Pathogenwatch is comparable to established bioinformatics methods, and that genomic predictions of AMR are highly concordant with phenotypic susceptibility data. We demonstrate the public health utility of Pathogenwatch with examples selected from >4,300 public genomes available in the application. Pathogenwatch provides an intuitive entry point to monitor of the emergence and spread of S. Typhi high risk clones.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Salmonella typhi/efectos de los fármacos , Fiebre Tifoidea/prevención & control , Proteínas Bacterianas/genética , Genoma Bacteriano/genética , Genómica/métodos , Genotipo , Geografía , Humanos , Malaui , Proteínas de Transporte de Membrana/genética , Pruebas de Sensibilidad Microbiana/métodos , Mutación , Salmonella typhi/genética , Salmonella typhi/fisiología , Tanzanía , Fiebre Tifoidea/microbiología
7.
BMC Infect Dis ; 21(1): 394, 2021 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-33926375

RESUMEN

BACKGROUND: Whole-genome sequencing has shown that the Mycobacterium tuberculosis infection process can be more heterogeneous than previously thought. Compartmentalized infections, exogenous reinfections, and microevolution are manifestations of this clonal complexity. The analysis of the mechanisms causing the microevolution -the genetic variability of M. tuberculosis at short time scales- of a parental strain into clonal variants with a patient is a relevant issue that has not been yet completely addressed. To our knowledge, a whole genome sequence microevolution analysis in a single patient with inadequate adherence to treatment has not been previously reported. CASE PRESENTATION: In this work, we applied whole genome sequencing analysis for a more in-depth analysis of the microevolution of a parental Mycobacterium tuberculosis strain into clonal variants within a patient with poor treatment compliance in Argentina. We analyzed the whole-genome sequence of 8 consecutive Mycobacterium tuberculosis isolates obtained from a patient within 57-months of intermittent therapy. Nineteen mutations (9 short-term, 10 fixed variants) emerged, most of them associated with drug resistance. The first isolate was already resistant to isoniazid, rifampicin, and streptomycin, thereafter the strain developed resistance to fluoroquinolones and pyrazinamide. Surprisingly, isolates remained susceptible to the pro-drug ethionamide after acquiring a frameshift mutation in ethA, a gene required for its activation. We also found a novel variant, (T-54G), in the 5' untranslated region of whiB7 (T-54G), a region allegedly related to kanamycin resistance. Notably, discrepancies between canonical and phage-based susceptibility testing to kanamycin were previously found for the isolate harboring this mutation. In our patient, microevolution was mainly driven by drug selective pressure. Rare short-term mutations fixed together with resistance-conferring mutations during therapy. CONCLUSIONS: This report highlights the relevance of whole-genome sequencing analysis in the clinic for characterization of pre-XDR and MDR resistance profile, particularly in patients with incomplete and/or intermittent treatment.


Asunto(s)
Farmacorresistencia Bacteriana Múltiple/genética , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Adulto , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Argentina , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Femenino , Humanos , Isoniazida/uso terapéutico , Cumplimiento de la Medicación , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium tuberculosis/aislamiento & purificación , Filogenia , Pirazinamida/uso terapéutico , Rifampin/uso terapéutico , Estreptomicina/farmacología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Secuenciación Completa del Genoma
8.
BMC Infect Dis ; 21(1): 330, 2021 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-33832459

RESUMEN

OBJECTIVES: To explore the drug susceptibility of levofloxacin (LFX), moxifloxacin (MFX), bedaquiline (BDQ), linezolid (LZD), clofazimine (CFZ) and delamanid (DLM) against multidrug resistant tuberculosis (MDR-TB) isolates from drug resistance survey of southwest China, and to illustrate the genetic characteristics of MDR-TB isolates with acquired drug resistance. METHODS: A total of 339 strains were collected from smear-positive TB patients in the drug resistance survey of southwest China between January 2014 and December 2016. The MICs for the above mentioned drugs were determined for MDR-TB by conventional drug susceptibility testing. Genes related to drug resistance were amplified with their corresponding pairs of primers. RESULTS: MDR was observed in 88 (26.0%; 88/339) isolates. LFX had the highest resistance rate (50.0%; 44/88), followed by MFX (38.6%; 34/88). The resistance rate to LZD, CFZ, and DLM was 4.5% (4/88), 3.4% (3/88), and 4.5% (4/88), respectively, and the lowest resistance rate was observed in BDQ (2.3%; 2/88). Of the 45 isolates resistant to LFX and MFX, the most prevalent resistance mutation was found in gyrA with the substitution of codon 94 (34/45, 75.6%). Two strains with CFZ - BDQ cross resistance had a mutation in the Rv0678 gene. Of the four LZD resistant isolates, two carried mutations in rplC gene. For the four isolates resistant to DLM, one isolate had mutations in codon 318 of fbiC gene, and two isolates were with mutations in codon 81 of ddn gene. CONCLUSION: This study provided evidence of the usefulness of new anti-TB drugs in the treatment of MDR-TB in China.


Asunto(s)
Antituberculosos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , China , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium tuberculosis/aislamiento & purificación
9.
BMC Infect Dis ; 21(1): 372, 2021 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-33882854

RESUMEN

BACKGROUND: Some Staphylococcus aureus strains produce Panton-Valentine leukocidin (PVL), a bi-component pore-forming toxin, which causes leukocyte lysis and tissue necrosis. Currently, there is very limited information on the molecular epidemiology of PVL-encoding S. aureus strains in Iran. This study aimed to determine the molecular epidemiology and genetic background of PVL-positive S. aureus clinical strains isolated from Iranian patients. METHODS: A total of 28 PVL-positive S. aureus strains were detected from 600 S. aureus isolates between February 2015 and March 2018 from different hospitals in Tehran, Iran. Antimicrobial susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Molecular genotyping was performed using SCCmec and accessory gene regulator (agr) typing, PVL haplotyping, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). RESULTS: The highest antibiotic resistance rate was found to be against erythromycin (57.1%), followed by ciprofloxacin (42.8%) and clindamycin (35.7%). Moreover, 19 (67.9%) out of 28 S. aureus isolates were identified as MRSA, including CA-MRSA (14/19, 73.7%) and HA-MRSA (5/19, 26.3%). SCCmec type IVa was detected as the predominant type (10/19, 52.6%), followed by type III (5/19, 26.3%) and type V (4/19, 21.1%). The agr type I was identified as the most common type (14/28, 50%), and H and R haplotype groups were observed at frequencies of 67.9 and 32.1%, respectively. Among H variants, the predominant variant was H2 (78/9%). The isolates encompassed 21 different sequence types (STs), including 16 new STs (ST5147 to ST5162). Based on eBURST analysis, the isolates were clustered into five CCs, including CC30, CC22, CC1, CC8, and CC5 (ST5160), and nine singletons. PFGE typing showed that 24 isolates were clustered into A (4 pulsotypes), B (9 pulsotypes), and C (11 pulsotypes) clusters. CONCLUSIONS: A high prevalence of PVL-positive CA-MRSA strains was detected in Iran. The majority of PVL-positive isolates were of H (mostly H2) variant, while R variant was harbored by 100% of PVL-positive MRSA strains. Also, CC8, CC22, and CC30 were identified as the dominant clones among PVL-encoding S. aureus strains. This study promotes a better understanding of the molecular epidemiology and evolution of PVL-positive S. aureus strains in Iran.


Asunto(s)
Toxinas Bacterianas/genética , Exotoxinas/genética , Haplotipos , Leucocidinas/genética , Staphylococcus aureus Resistente a Meticilina/genética , Polimorfismo de Nucleótido Simple , Infecciones Estafilocócicas/epidemiología , Antibacterianos/uso terapéutico , Toxinas Bacterianas/metabolismo , Farmacorresistencia Bacteriana Múltiple/genética , Electroforesis en Gel de Campo Pulsado , Exotoxinas/metabolismo , Genómica , Humanos , Irán/epidemiología , Leucocidinas/metabolismo , Masculino , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/metabolismo , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Filogenia , Prevalencia , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología
10.
J Med Microbiol ; 70(4)2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33826489

RESUMEN

As the representative multidrug-resistant pathogen, Stenotrophomonas maltophilia has multiple intrinsic and acquired resistances, including carbapenem resistance. In companion animals, the antimicrobial susceptibility and sequence types (STs) of S. maltophilia are not well understood due to its limited isolation rate. We investigated the antimicrobial susceptibilities and multilocus sequence types (MLSTs) of 38 S. maltophilia strains isolated from dogs and cats in Japan. Prevalence of resistance was detected for imipenem (100 %), aztreonam (94.7 %), piperacillin (65.8 %), trimethoprim-sulfamethoxazole (65.8 %), and ceftazidime (60.5 %). Rates of resistances to chloramphenicol, minocycline, and levofloxacin were low (2.6-5.3 %). MLST analysis revealed that all 38 strains were assigned to 34 STs, including 11 previously reported STs and 23 newly identified STs. Phylogenetic analysis of MLSTs enabled categorization of 13 isolates (34.2 %) into genogroup 6, which is a major genogroup of human isolates. Multinational surveillance would be needed to clarify the significance of antimicrobial-resistant S. maltophilia isolates from companion animals.


Asunto(s)
Enfermedades de los Gatos/microbiología , Enfermedades de los Perros/microbiología , Farmacorresistencia Bacteriana Múltiple/genética , Infecciones por Bacterias Gramnegativas/veterinaria , Stenotrophomonas maltophilia/efectos de los fármacos , Animales , Antibacterianos/uso terapéutico , Enfermedades de los Gatos/tratamiento farmacológico , Gatos , Enfermedades de los Perros/tratamiento farmacológico , Perros , Genotipo , Infecciones por Bacterias Gramnegativas/microbiología , Japón , Tipificación de Secuencias Multilocus , Stenotrophomonas maltophilia/clasificación
11.
Int J Mol Sci ; 22(8)2021 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-33920239

RESUMEN

Post-weaning diarrhea due to enterotoxigenic Escherichia coli (ETEC) is a common disease of piglets and causes great economic loss for the swine industry. Over the past few decades, decreasing effectiveness of conventional antibiotics has caused serious problems because of the growing emergence of multidrug-resistant (MDR) pathogens. Various studies have indicated that antimicrobial peptides (AMPs) have potential to serve as an alternative to antibiotics owing to rapid killing action and highly selective toxicity. Our previous studies have shown that AMP GW-Q4 and its derivatives possess effective antibacterial activities against the Gram-negative bacteria. Hence, in the current study, we evaluated the antibacterial efficacy of GW-Q4 and its derivatives against MDR ETEC and their minimal inhibition concentration (MIC) values were determined to be around 2~32 µg/mL. Among them, AMP Q4-15a-1 with the second lowest MIC (4 µg/mL) and the highest minimal hemolysis concentration (MHC, 256 µg/mL), thus showing the greatest selectivity (MHC/MIC = 64) was selected for further investigations. Moreover, Q4-15a-1 showed dose-dependent bactericidal activity against MDR ETEC in time-kill curve assays. According to the cellular localization and membrane integrity analyses using confocal microscopy, Q4-15a-1 can rapidly interact with the bacterial surface, disrupt the membrane and enter cytosol in less than 30 min. Minimum biofilm eradication concentration (MBEC) of Q4-15a-1 is 4× MIC (16 µg/mL), indicating that Q4-15a-1 is effective against MDR ETEC biofilm. Besides, we established an MDR ETEC infection model with intestinal porcine epithelial cell-1 (IPEC-1). In this infection model, 32 µg/mL Q4-15a-1 can completely inhibit ETEC adhesion onto IPEC-1. Overall, these results suggested that Q4-15a-1 may be a promising antibacterial candidate for treatment of weaned piglets infected by MDR ETEC.


Asunto(s)
Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Escherichia coli Enterotoxigénica/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Proteínas Citotóxicas Formadoras de Poros/farmacología , Enfermedades de los Porcinos/tratamiento farmacológico , Animales , Antibacterianos/efectos adversos , Antibacterianos/farmacología , Adhesión Bacteriana/efectos de los fármacos , Biopelículas/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Escherichia coli Enterotoxigénica/patogenicidad , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/veterinaria , Pruebas de Sensibilidad Microbiana , Porcinos/microbiología , Enfermedades de los Porcinos/microbiología , Enfermedades de los Porcinos/patología
12.
Rev Chilena Infectol ; 38(1): 69-80, 2021 Feb.
Artículo en Español | MEDLINE | ID: mdl-33844795

RESUMEN

Pseudomonas aeruginosa is one of the major pathogens causing healthcare-associated infections (HAI). Its capacity of adaptation, dissemination, intrinsic resistance to antimicrobials and of acquiring new mechanisms through mobile genetic elements, make the treatment of infections by this microorganism a challenge for the clinician. Intrinsically, P. aeruginosa, presents a reduced permeability in the external membrane, due to the expression of efflux pumps, and an inducible AmpC-type cephalosporinase. In addition, P. aeruginosa is able to acquire new resistance determinants by horizontal transfer in the form of cassettes located in integrons, and in turn located in transposons or plasmids. Within the enzymatic resistance that P. aeruginosa presents, betalactamases, including extended spectrum (ESBL) and carbapenemases. But also aminoglycoside modifying enzymes, stand out, causing this microorganism to present multi-resistance phenotypes (MDR), extreme resistance (XDR) and pan-resistance (PDR) to the called antipseudomonal antibiotics, including the new cephalosporins with betalactamase inhibitors.


Asunto(s)
Infecciones por Pseudomonas , Pseudomonas aeruginosa , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Humanos , Laboratorios , Pruebas de Sensibilidad Microbiana , Plásmidos , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/genética , beta-Lactamasas/genética
13.
J Med Microbiol ; 70(4)2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33830906

RESUMEN

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options.Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited.Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae.Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR.Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (ß-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible.Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae, harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Enterobacteriaceae/efectos de los fármacos , Nitrofurantoína/farmacología , Proteínas Bacterianas/genética , Farmacorresistencia Bacteriana Múltiple/genética , Enterobacteriaceae/genética , Enterobacteriaceae/aislamiento & purificación , Enterobacteriaceae/fisiología , Infecciones por Enterobacteriaceae/microbiología , Humanos , Pruebas de Sensibilidad Microbiana
14.
Nat Commun ; 12(1): 2460, 2021 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-33911082

RESUMEN

It is well established that antibiotic treatment selects for resistance, but the dynamics of this process during infections are poorly understood. Here we map the responses of Pseudomonas aeruginosa to treatment in high definition during a lung infection of a single ICU patient. Host immunity and antibiotic therapy with meropenem suppressed P. aeruginosa, but a second wave of infection emerged due to the growth of oprD and wbpM meropenem resistant mutants that evolved in situ. Selection then led to a loss of resistance by decreasing the prevalence of low fitness oprD mutants, increasing the frequency of high fitness mutants lacking the MexAB-OprM efflux pump, and decreasing the copy number of a multidrug resistance plasmid. Ultimately, host immunity suppressed wbpM mutants with high meropenem resistance and fitness. Our study highlights how natural selection and host immunity interact to drive both the rapid rise, and fall, of resistance during infection.


Asunto(s)
Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Meropenem/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Selección Genética/genética , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas Bacterianas/genética , Humanos , Hidroliasas/genética , Proteínas de Transporte de Membrana/genética , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Plásmidos/genética , Porinas/genética , Infecciones por Pseudomonas/patología , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/inmunología , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/microbiología , Análisis de Secuencia de ADN , Choque Hemorrágico/microbiología
15.
J Med Microbiol ; 70(3)2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33739918

RESUMEN

Introduction. Carbapenem resistance in Acinetobacter baumannii (A. baumannii) is an emerging global threat.Gap statement. The adaptation strategies of A. baumannii for this emergence as a nosocomial pathogen has been less studied.Aim. This prospective study analysed a sustained outbreak of carbapenem resistant Acinetobacter baumannii (CRAB) in the intensive care unit (ICU) with reference to antimicrobial resistance and virulence in the colonizing and pathogenic isolates under carbapenem stress.Results. The CRAB isolates from initial and sustained outbreak were found harbouring multiple carbapenemase genes. These genes included bla OXA-23 ,bla IMP, bla VIM and bla NDM. From NICU environment three phenotypically carbapenem susceptible isolates were found carrying bla OXA-23, bla IMP, bla VIM genes. Prior imipenem therapy was one of the risk factors (P=0.0016). The outbreak was polyclonal. Under imipenem stress, outbreak isolates showed no loss of carbapenemase genes against stress free conditions (23.7±1.33 days). Biofilm formation increased with imipenem concentration, with outbreak isolates producing highest biomass. While the pathogens showed a slow growth rate on imipenem exposure, the colonisers grew rapidly (P <0.0001).Methods. Sustained outbreak of CRAB was identified in the ICU (July 2015 to December 2017). Risk factors for acquisition of CRAB was studied. A. baumannii isolates were also collected from the environments of ICU and neonatal ICU (NICU) and blood cultures of septic neonates. Isolates were characterized based on antimicrobial susceptibility, genetic profile, integrons carriage and clonality. Biofilm formation and growth kinetics were studied under varying carbapenem stress.Conclusion. Intense carbapenem exposure in the ICU facilitates persistence of CRAB by several adaptations causing sustained outbreaks.


Asunto(s)
Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/fisiología , Adaptación Fisiológica , Carbapenémicos/farmacología , Infección Hospitalaria/microbiología , Brotes de Enfermedades , Farmacorresistencia Bacteriana Múltiple/fisiología , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/epidemiología , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/patogenicidad , Adulto , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Carbapenémicos/uso terapéutico , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/epidemiología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Microbiología Ambiental , Femenino , Genes Bacterianos , Humanos , Imipenem/farmacología , Imipenem/uso terapéutico , Integrones/genética , Unidades de Cuidados Intensivos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Virulencia , beta-Lactamasas/genética , beta-Lactamasas/metabolismo
16.
J Med Microbiol ; 70(3)2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33750516

RESUMEN

Introduction. The possible transfer of antimicrobial resistance genes between Enterococcus faecium isolates from humans and different animal species, including those not covered by monitoring programs (e.g. pet and wildlife), poses a serious threat to public health.Hypothesis/Gap Statement. Little is known about occurrence and mechanisms of phenomenon of multidrug resistance of E. faecium isolated from various host species in Poland.Aim. The aim of the study was to characterize multidrug-resistant E. faecium isolated from humans and animals (livestock, pets and wildlife) in terms of the occurrence of genetic markers determining resistance.Methodology. Bacterial isolates were tested for phenotypic resistance and the presence of genes encoding resistance to macrolides, tetracycline, aminoglycosides, aminocyclitols and phenicols as well as efflux pump (emeA), resolvase (tndX) and integrase (Int-Tn) genes. The quinolone resistance-determining regions of gyrA and parC were sequenced.Results. Human isolates of E. faecium were characterized by high-level resistance to: ciprofloxacin, enrofloxacin, erythromycin (100 %), as well, as aminoglycosides resistance (kanamycin - 100%, streptomycin - 78 %, gentamicin - 78%). Regardless of the animal species, high level of resistance of E. faecium to tetracycline (from 88-100 %), erythromycin (from 82-94 %) and kanamycin (from 36-100 %) was observed. All E. faecium isolates from wildlife were resistant to fluoroquinolones. However, full susceptibility to vancomycin was observed in all isolates tested. Phenotypic antimicrobial resistance of E. faecium was identified in the presence of the following resistance genes: erm(B) (70%), msr(A) (50 %), tet(L) (35 %), tet(K) (34 %), tet(M) (76 %), aac(6')-Ie-aph(2″)-Ia (25%), ant(6)-Ia (31%), aph(3)-IIIa (68 %), (tndX) (23 %), and integrase gene (Int-Tn) (34 %). A correlation between an amino acid substitution at positions 83 and 87 of gyrA and position 80 of parC and the high-level fluoroquinolone resistance in E. faecium has been observed as well.Conclusion. The level and range of antimicrobial resistance and the panel of resistance determinants is comparable between E. faecium isolates, despite host species.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Enterococcus faecium/aislamiento & purificación , Enterococcus faecium/fisiología , Infecciones por Bacterias Grampositivas/microbiología , Animales , Elementos Transponibles de ADN , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Enterococcus faecium/efectos de los fármacos , Enterococcus faecium/genética , Genes Bacterianos/genética , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Polonia/epidemiología
17.
Int J Infect Dis ; 105: 695-701, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33676003

RESUMEN

OBJECTIVES: The emergence and spread of nonencapsulated Streptococcus pneumoniae (NESp) is a public health concern in the post-pneumococcal conjugate vaccine era. We analyzed the prevalence, molecular characteristics, and antimicrobial resistance of NESp responsible for noninvasive infections in northern Japan. METHODS: NESp isolates were identified using molecular and phenotypical methods among 4463 S. pneumoniae isolates from noninvasive infection cases during 4 study periods between January 2011 and January 2019. NESp isolates were analyzed for antimicrobial susceptibility, genotype, and virulence-associated genes. RESULTS: Seventy-one NESp isolates were identified (1.6% of total clinical isolates) and assigned to the null capsule clade (NCC)1 (pspK+) (94.4%) or NCC2 (aliC+/aliD+) (5.6%). The dominant sequence types (STs) were ST7502 (23.9%), ST4845 (19.7%), ST16214 (11.3%), ST11379 (9.9%), and ST7786 (7.0%). These 5 dominant STs and all 7 novel STs were related to the sporadic NESp lineage ST1106 or PMEN clone Denmark14-ST230. High non-susceptibility rates of NESp were observed for trimethoprim-sulfamethoxazole, erythromycin, and tetracycline (>92.9%), and multidrug resistance was observed in 88.7% of the NESp isolates, including all ST7502, ST4845, and ST11379 isolates. CONCLUSIONS: The study revealed that the dominant clonal groups of NESp were associated with a high prevalence of non-susceptibility to antimicrobials in northern Japan.


Asunto(s)
Farmacorresistencia Bacteriana/genética , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Streptococcus pneumoniae/genética , Adolescente , Adulto , Antibacterianos/uso terapéutico , Niño , Farmacorresistencia Bacteriana Múltiple/genética , Humanos , Japón/epidemiología , Pruebas de Sensibilidad Microbiana/métodos , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/genética , Prevalencia , Streptococcus pneumoniae/aislamiento & purificación , Vacunas Conjugadas/uso terapéutico , Virulencia , Factores de Virulencia/genética
18.
Int J Tuberc Lung Dis ; 25(4): 285-291, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33762072

RESUMEN

BACKGROUND: TB is the leading cause of death from a single infectious disease, particularly among people living with HIV (PLHIV). Molecular epidemiology provides information on prevalent genotypes of Mycobacterium tuberculosis and disease transmission dynamics, which aid in TB control. Identification of mutations that confer drug resistance is essential for the rapid diagnosis of drug-resistant TB, especially in high TB burden settings, like the Philippines.METHODS: This study aimed to determine mutations in M. tuberculosis drug resistance-conferring genes and circulating genotypes in PLHIV. MIRU-VNTR (mycobacterial interspersed repetitive unit-variable number of tandem repeats) typing using a set of 24-loci and sequencing of drug resistance-conferring genes were performed in 22 M. tuberculosis isolates from TB-HIV co-infected patients.RESULTS: The prevalence of resistance to any drug was 31.8%, 18.2% for isoniazid monoresistance, 4.5% for streptomycin monoresistance and 9.1% for multidrug resistance. The identified mutations in the katG, rpoB, pncA, rpsL and gyrA genes have been reported in the literature; none was found in the inhA and embB genes. All isolates belonged to the EAI2-Manila family and were grouped into four clusters based on their phenotypic drug resistance and mutation profiles.CONCLUSION: The use of 24-loci set may be used as a more discriminatory MIRU-VNTR typing in settings where the East African-Indian lineage is predominant, like the Philippines.


Asunto(s)
Coinfección , Infecciones por VIH , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Adulto , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Coinfección/tratamiento farmacológico , Coinfección/epidemiología , Farmacorresistencia Bacteriana Múltiple/genética , Genotipo , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular , Mutación , Mycobacterium tuberculosis/genética , Filipinas/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología
19.
Int J Food Microbiol ; 344: 109116, 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33676332

RESUMEN

Staphylococcus aureus is among the most common zoonotic pathogens originating from animals consumed as food, especially raw chicken meat (RCM). As far as we know, this might be the first report that explores the efficacy of metal oxide nanoparticles (MONPs), such as zinc peroxide nanoparticles (ZnO2-NPs), zinc oxide nanoparticles (ZnO-NPs), and titanium dioxide nanoparticles (TiO2-NPs) against multidrug resistant (MDR) and/or pandrug resistant (PDR) S. aureus strains with a strong biofilm-producing ability isolated from RCM and giblets. The overall prevalence of coagulase-positive staphylococci was 21%, with a contamination level range between 102 and 104 CFU/g. The incidence of virulence genes See (21/36), pvl (16/36), clfA (15/36), sec (12/36), tst (12/36), and sea (11/36) among S. aureus strains were relatively higher those of seb, sed, fnbA, and fnbB. For antimicrobial resistance gene distribution, most strains harbored the blaZ gene (25/36), aacA-aphD gene (24/36), mecA gene (22/36), vanA gene (20/36), and apmA gene (20/36) confirmed the prevalence of MDR among S. aureus of RCM products. However, cfr (11/36), spc (9/36), and aadE (7/36) showed a relatively lower existence. The data of antibiogram resistance profiles was noticeably heterogeneous (25 patterns) with 32 MDR and four PDR S. aureus strains. All tested strains had a very high MAR index value (>0.2) except the P11 pattern (GEN, MXF, PMB), which showed a MAR index of 0.19. Among the strong biofilm-producing ability (BPA), 14 (70%) strains were isolated from wet markets, while only six strong BPA strains were isolated from supermarkets. The mean values of BPA ranged from 2.613 ± 0.04 to 11.013 ± 0.05. Clearly, ZnO2-NPs show significant inhibitory activity against S. aureus strains compared with those produced by the action of ZnO-NPs and TiO2-NPs. The results of anti-inflammatory activity suggest ZnO2-NPs as a lead compound for designing an alternative antimicrobial agent against drug-resistant and strong biofilm-producing S. aureus isolates from retail RCM and giblets.


Asunto(s)
Antibacterianos/farmacología , Contaminación de Alimentos/prevención & control , Staphylococcus aureus/crecimiento & desarrollo , Titanio/farmacología , Óxido de Zinc/farmacología , Animales , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Pollos/microbiología , Farmacorresistencia Bacteriana Múltiple/genética , Contaminación de Alimentos/análisis , Microbiología de Alimentos , Carne/microbiología , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/prevención & control , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Virulencia/genética
20.
Artículo en Inglés | MEDLINE | ID: mdl-33787739

RESUMEN

The emergence and spread of extensively drug-resistant tuberculosis (XDR-TB) is a serious threat to global health. Therefore, its rapid diagnosis is crucial. The present study aimed to characterize mutations conferring resistance to second line drugs (SLDs) within multidrug Mycobacterium tuberculosis (MDR-MTB) isolates and to estimate the occurrence of XDR-TB in Casablanca, Morocco. A panel of 200 MDR-TB isolates was collected at the Pasteur Institute between 2015-2018. Samples were subjected to drug susceptibility testing to Ofloxacin (OFX), Kanamycin (KAN) and Amikacin (AMK). The mutational status of gyrA, gyrB, rrs, tlyA and eis was assessed by sequencing these target genes. Drug susceptibility testing for SLDs showed that among the 200 MDR strains, 20% were resistant to OFX, 2.5% to KAN and 1.5% to AMK. Overall, 14.5% of MDR strains harbored mutations in gyrA, gyrB, rrs and tlyA genes. From the 40 OFXR isolates, 67.5% had mutations in QRDR of gyrA and gyrB genes, the most frequent one being Ala90Val in gyrA gene. Of note, none of the isolates harbored simultaneously mutations in gyrA and gyrB genes. In eight out of the 200 MDR-TB isolates resistant either to KAN or AMK, only 25% had A1401G or Lys89Glu change in rrs and tlyA genes respectively. This study is very informative and provides data on the alarming rate of fluoroquinolone resistance which warrants the need to implement appropriate drug regimens to prevent the emergence and spread of more severe forms of Mycobacterium tuberculosis drug resistance.


Asunto(s)
Antituberculosos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/genética , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Adulto , Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Femenino , Técnicas de Genotipaje , Humanos , Masculino , Pruebas de Sensibilidad Microbiana/métodos , Persona de Mediana Edad , Marruecos/epidemiología , Mutación/genética , Mycobacterium tuberculosis/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Análisis de Secuencia de ADN , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología
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