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OBJECTIVES: The prognosis of bone and joint infections (BJI) caused by Gram-negative bacilli (GNB) worsens significantly in the face of fluoroquinolone-resistance. In this setting, scarce pre-clinical and clinical reports suggest that intravenous beta-lactams plus colistin may improve outcome. Our aim was to assess the efficacy and safety of this treatment in a well-characterized prospective cohort. METHODS: Observational, prospective, non-comparative, multicenter (14 hospitals) study of adults with BJI caused by fluoroquinolone-resistant GNB treated with surgery and intravenous beta-lactams plus colistin for ≥ 21 days. The primary endpoint was the cure rate. RESULTS: Of the 44 cases included (median age 72 years [IQR 50-81], 22 [50%] women), 32 (73%) had an orthopedic device-related infection, including 17 (39%) prosthetic joints. Enterobacterales were responsible for 27 (61%) episodes, and Pseudomonas spp for 17 (39%), with an overall rate of MDR/XDR GNB infections of 27/44 (61%). Patients were treated with colistin plus intravenous beta-lactam for 28 days (IQR 22-37), followed by intravenous beta-lactam alone for 19 days (IQR 5-35). The cure rate (intention-to-treat analysis; median follow-up = 24 months, IQR 19-30) was 82% (95% CI 68%-90%) and particularly, 80% (95% CI 55%-93%) among patients managed with implant retention. Adverse events (AEs) leading to antimicrobial withdrawal occurred in 10 (23%) cases, all of which were reversible. Colistin AEs were associated with higher plasma drug concentrations (2.8 mg/L vs. 0.9 mg/L, p = 0.0001). CONCLUSIONS: Combination therapy with intravenous beta-lactams plus colistin is an effective regimen for BJI caused by fluoroquinolone-resistant GNB. AEs were reversible and potentially preventable by close therapeutic drug monitoring.
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PURPOSE: Infections caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp (ESKAPE) plus Escherichia coli (E2SKAPE), in particular multidrug-resistant (MDR) E2SKAPE infections, occur frequently and pose a life-threatening to liver transplant (LT) recipients. To prevent E2SKAPE infections and improve the prognosis of LT recipients, the identification of risk factors for E2SKAPE infections and mortality is necessary. METHODS: E2SKAPE pathogens were isolated and identified from clinical samples following standard microbiological procedures. All episodes of E2SKAPE infections and mortality documented among LT recipients were analyzed. FINDINGS: A total of 83 episodes of E2SKAPE infections, including 75 (90.4%) episodes of MDR-E2SKAPE infections, occurred in 23.1% (53/229) of LT recipients. E. faecium was the dominant causative bacterium (37/83; 44.6%). The most common site of infections was the urinary tract (14/53; 26.4%). Sixteen (7%) patients died within 2 months after LT, and 7 deaths were E2SKAPE infections-related. Multivariate logistic regression analysis revealed that female sex [odds ratio (OR) = 3.665, 95% confidence interval (CI): 1.614-8.321, P = 0.002], duration of surgery ≥ 400 min [OR = 2.328, 95%CI: 1.151-4.707, P = 0.019], intraoperative red blood cell (RBC) transfusion ≥ 12U [OR = 2.542, 95%CI: 1.218-5.306, P = 0.013] and indwelling urethral catheter use ≥ 3 days [OR = 3.96, 95%CI: 1.309-11.981, P = 0.015] were independent risk factors for E2SKAPE infections after LT, and that only exposure to more than 2 intravenous antibiotics post-LT [OR = 0.318, 95%CI: 0.15-0.674, P = 0.003] was negatively associated with acquisition of E2SKAPE infections. The predictors of crude mortality included female sex [OR = 4.822, 95%CI: 1.299-17.904, P = 0.019], creatinine on day 3 post-LT > 1.5 mg/dL [OR = 11.014, 95%CI: 2.985-40.637, P < 0.001], mechanical ventilation post-LT [OR = 10.724, 95%CI: 2.695-42.676, P = 0.001] and recipients with E2SKAPE infections [OR = 4.112, 95%CI: 1.169-14.47, P = 0.028]. IMPLICATIONS: A high incidence of E2SKAPE infections was noted in the early post-LT period. The most common infection site was the urinary tract, and the dominant pathogenic bacterium was E. faecium. Female sex, prolonged surgery time, massive RBC transfusion, or delayed urethral catheter removal were associated with E2SKAPE infections. Only exposure to more than 2 intravenous antibiotics post-LT was negatively related to the acquisition of E2SKAPE infections. The predictors of mortality included female sex, creatinine on day 3 post-LT>1.5 mg/dL, mechanical ventilation post-LT, and recipients with E2SKAPE infections.
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Infections caused by bacteria that are resistant to many drugs are a major threat to public health in many countries around the world. Here we demonstrate the creation of heterogeneous catalytic nanomaterials with outstanding antimicrobial properties against several superbugs. We have shown that replacing a small amount of copper in a generated copper-phosphate-enzyme nanoflower hybrid with silver drastically increases the antimicrobial capacity of the nanomaterial. In this sense, it has been confirmed that the exchange generated silver phosphate nanoparticles on the Cu nanoflowers, with control of the nanoparticle diameter size. The Fenton catalytic activity of the Ag-containing nanobiohybrids was affected, showing better performance with lower amounts of silver in the final hybrid. This effect was confirmed by their antimicrobial efficacy against Escherichia coli, where the Ag4Cu32@CALB hybrid displayed a log reduction of 3.9, an efficiency more than 5000 times higher than that obtained with copper nanoflowers (Cu36@CALB). The hybrid also showed excellent efficacy against other bacteria such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and Mycobacterium smegmatis with log reductions of 7.6, 4.3, and 1.8, respectively.
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Multidrug-resistant (MDR) bacterial infections are becoming a life-threatening issue in public health; therefore, it is urgent to develop novel antibacterial agents for treating infections caused by MDR bacteria. The 20(S)-protopanaxadiol (PPD) derivative 9 was identified as a novel antibacterial hit compound in screening of our small synthetic natural product-like (NPL) library. A series of novel PPD derivatives with heterocyclic rings fused at the C-2 and C-3 positions of the A-ring were synthesized and their antibacterial activities against Staphylococcus aureus (S. aureus) Newman strain and MDR S. aureus strains (USA300, NRS-1, NRS-70, NRS-100, NRS-108, NRS-271, XJ017, and XJ036) were evaluated. Among these compounds, quinoxaline derivative 56 (SH617) exhibited the highest activity with MICs of 0.5-4 µg/mL against the S. aureus Newman strain and the eight MDR S. aureus strains. Its antibacterial activity was comparable to that of the positive control, vancomycin. In the zebrafish, 56 revealed no obvious toxicity even at a high administered dose. In vivo, following a lethal infection induced by USA300 strains in zebrafish, 56 exhibited significantly increased survival rates in a dose-dependent manner.
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Antibacterianos , Pruebas de Sensibilidad Microbiana , Sapogeninas , Staphylococcus aureus , Pez Cebra , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Sapogeninas/farmacología , Sapogeninas/química , Sapogeninas/síntesis química , Staphylococcus aureus/efectos de los fármacos , Animales , Relación Estructura-Actividad , Estructura Molecular , Relación Dosis-Respuesta a Droga , Compuestos Heterocíclicos/farmacología , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/síntesis químicaRESUMEN
BACKGROUND: Bacteriophage has been renewed attention as a new antibacterial agent due to the limitations of antibiotic treatment. Bacteriophages are generally thought to be highly host specific and even strain specific, but a small number of polyvalent bacteriophages have been found to infect bacteria of different genera. RESULTS: In this study, a virulent lytic bacteriophage (named Salmonella phage PSH-1) of Salmonella Enteritidis was isolated from the sewage samples of a large-scale pig farm, PSH-1 demonstrated lytic activity against four multidrug-resistant Salmonella Enteritidis isolates and Escherichia coli, and then its biological characteristics, genome and bacteriostatic ability were investigated. The results showed that the initial titer of PSH-1 was 1.15 × 1010 PFU/mL and the optimal multiplicity of infection (MOI) was 0.01, PSH-1 has stable activity in the range of pH 3.0-11.0. One-step growth curve showed that its latent period was 20 min, burst time was 80 min, and the burst was 495 particles. The whole-genome sequencing results revealed phage PSH-1 had a linear dsDNA with 48,466 bp length. The G/C content was 45.33%. Non-coding RNA genes and virulence factors were not found. Eighty- five open reading frames (ORFs) were identified after online annotation. By tests, the use of phage could succeed in controlling the artificial Salmonella contamination in milk at a range of temperatures. CONCLUSIONS: This study reports a novel Salmonella Enteritidis phage PSH-1, which has a robust lytic ability, no virulence factors, and good stability. The characterization and genomic analysis of PSH-1 will develop our understanding of phage biology and diversity and provide a potential arsenal for controlling of salmonellosis.
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Farmacorresistencia Bacteriana Múltiple , Genoma Viral , Fagos de Salmonella , Salmonella enteritidis , Aguas del Alcantarillado , Secuenciación Completa del Genoma , Salmonella enteritidis/virología , Salmonella enteritidis/genética , Salmonella enteritidis/efectos de los fármacos , Fagos de Salmonella/genética , Fagos de Salmonella/aislamiento & purificación , Fagos de Salmonella/fisiología , Fagos de Salmonella/clasificación , Farmacorresistencia Bacteriana Múltiple/genética , Animales , Aguas del Alcantarillado/virología , Aguas del Alcantarillado/microbiología , Porcinos , Composición de Base , Escherichia coli/virología , Escherichia coli/genéticaRESUMEN
The increasing incidence of multidrug-resistant tuberculosis (MDR-TB) is one of the most challenging tasks in tuberculosis treatment. Conventional TB treatment regimens have proven ineffective in treating MDR-TB, thus demanding the development of new drugs followed by delivery systems. Bedaquiline, a novel anti-TB drug, has been reported to inhibit the ATP synthase required for the growth and replication of TB bacteria. Bedaquiline is able to target the persistent or latent form of TB, which remains difficult to treat with conventional drugs. This makes bedaquiline an important drug in the fight against MDR-TB. The drug has been approved by the US FDA as well as European Medicines Agency and is now widely used as part of combination therapy for the treatment of MDR-TB. Bedaquiline and its ad-vanced drug delivery system play a key role in tackling MDR-TB, providing a much-needed boost to control and eventually eliminate the disease. However, the cost of the drug remains a concern, and efforts are underway to make bedaquiline more accessible and affordable to patients in resource-limited settings. Nevertheless, the development of bedaquiline nanofor-mulations represents a significant step forward in the fight against TB and offers hope to millions of patients across the globe.
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BACKGROUND: Acinetobacter baumannii (A. baumannii) is a life-threatening and challenging pathogen. In addition, it accounts for numerous serious infections, particularly among immunocompromised patients. Resistance to nearly all clinically used antibiotics and their ability to spread this resistance is one of the most important concerns related to this bacterium. OBJECTIVES: This study describes different molecular mechanisms of two multidrug-resistant A. baumannii isolates obtained from endotracheal aspirates collected from the neonatal intensive care unit (NICU), Ain Shams University Hospital, Egypt. METHODS: Following the identification of two isolates, they were examined for susceptibility to antimicrobial agents. This was followed by multilocus sequence typing as well as whole-genome sequence (WGS). Additionally, a Pathosystems Resources Integration Center (PATRIC) analysis was performed. RESULTS: Two isolates, Ab119 and Ab123, exhibited resistance to all tested antibiotics except for tigecycline and colistin. The WGS analysis of antimicrobial resistance genes (AMR) indicated that both isolates shared beta-lactam, aminoglycoside, macrolides, and sulfonamide resistance genes. Furthermore, each strain revealed different resistance genes such as blaNDM-1, blaNDM-10, OXA-64, aph (3')-VI, Tet-B in Ab119 strain and blaOXA-68, blaPER-1, blaPER-7, Tet-39 in Ab123 strain. Multiple efflux pump genes were detected. Multilocus sequence typing indicated that both isolates belong to the same sequence type (ST931), which belongs to international clone (IC3). Both isolates exhibited the presence of multiple mobile genetic elements (MGEs), but no plasmid was detected in either of them. CONCLUSIONS: A low prevalence of the IC3 sequence type was identified among two A. baumannii isolates obtained from the NICU in Egypt, exhibiting a high resistance level. Healthcare workers must have knowledge regarding the prevalence of A. baumannii among different populations in order to administer suitable treatment, improve patient outcomes, and apply effective infection control practices.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Genoma Bacteriano , Unidades de Cuidado Intensivo Neonatal , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Secuenciación Completa del Genoma , Acinetobacter baumannii/genética , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/aislamiento & purificación , Acinetobacter baumannii/clasificación , Humanos , Egipto/epidemiología , Farmacorresistencia Bacteriana Múltiple/genética , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/epidemiología , Antibacterianos/farmacología , Estudios Prospectivos , Recién Nacido , Genoma Bacteriano/genética , Estudios TransversalesRESUMEN
BACKGROUND: We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. METHODS: This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. RESULTS: Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI - 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). CONCLUSIONS: The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.
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Antituberculosos , Clofazimina , Cicloserina , Diarilquinolinas , Levofloxacino , Linezolid , Rifampin , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Masculino , Femenino , Adulto , Clofazimina/uso terapéutico , Clofazimina/administración & dosificación , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Linezolid/uso terapéutico , Linezolid/administración & dosificación , Diarilquinolinas/uso terapéutico , Diarilquinolinas/administración & dosificación , Persona de Mediana Edad , China/epidemiología , Cicloserina/uso terapéutico , Cicloserina/administración & dosificación , Levofloxacino/uso terapéutico , Levofloxacino/administración & dosificación , Antituberculosos/administración & dosificación , Antituberculosos/uso terapéutico , Rifampin/uso terapéutico , Rifampin/administración & dosificación , Estudios Prospectivos , Quimioterapia Combinada , Resultado del Tratamiento , Adulto Joven , AncianoRESUMEN
Vibrio alfacsensis is traditionally seen as an environmental symbiont within its genus, with no detailedly documented pathogenicity in marine aquaculture to date. This study delves into the largely unexplored pathogenic potential and emerging antibiotic resistance of V. alfacsensis. The VA-1 strain, isolated from recirculating aquaculture system (RAS) effluent of cultured turbot (Scophthalmus maximus), underwent comprehensive analysis including biochemical identification, antibiotic susceptibility testing and reinfection trials. The results confirmed VA-1's pathogenicity and significant multiple antibiotic resistance. VA-1 could induce systemic infection in turbot, with symptoms like kidney enlargement, exhibiting virulence comparable to known Vibrio pathogens, with an LD50 around 2.36 × 106 CFU/fish. VA-1's remarkable resistance phenotype (14/22) suggested potential for genetic exchange and resistance factor acquisition in aquaculture environments. Phylogenetic analysis based on 16S rDNA sequences and whole-genome sequencing has firmly placed VA-1 within the V. alfacsensis clade, while genome-wide analysis highlights its similarity and diversity in relation to strains from across the globe. VA-1 contained numerous replicons, indicating the possibility for the spread of resistance and virulence genes. This study suggests V. alfacsensis may acquire and transfer pathogenic and resistant traits through horizontal gene transfer, a likelihood intensified by changing environmental and aquaculture conditions, highlighting the need for vigilant pathogen monitoring and new non-antibiotic treatments.
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Antibacterianos , Acuicultura , Farmacorresistencia Bacteriana Múltiple , Enfermedades de los Peces , Peces Planos , Vibrio , Animales , Peces Planos/microbiología , Vibrio/efectos de los fármacos , Vibrio/genética , Vibrio/patogenicidad , Enfermedades de los Peces/microbiología , Farmacorresistencia Bacteriana Múltiple/genética , Antibacterianos/farmacología , Vibriosis/microbiología , Vibriosis/veterinaria , Filogenia , Virulencia , Pruebas de Sensibilidad Microbiana , ARN Ribosómico 16S/genéticaRESUMEN
Introduction. Proper management of multidrug-resistant tuberculosis is a prioritized strategy for tuberculosis control worldwide. Objective. To evaluate differences concerning demographic and clinical characteristics and programmatic indicators of Buenaventura patient cohort with confirmed diagnosis of multidrug-resistant tuberculosis, compared to those of the other municipalities from Valle del Cauca, Colombia, 2013-2016. Materials and methods. We conducted an analytical cohort study to compare records of patients older than 15 years with multidrug-resistant tuberculosis included in the Programa de Tuberculosis de Buenaventura (with para-aminosalicylic acid) versus the other municipalities of Valle del Cauca (without para-aminosalicylic). Results. Ninety-nine cases were recorded with a median age of 40 years (IQR = 26 - 53); in Buenaventura, 56% of the patients were women, while in the other municipalities, men predominated with 67%; 95% had health insurance. The most common comorbidity was diabetes (14%). Adverse reactions to antituberculosis medications in Buenaventura were 1.3 times more frequent than in the other municipalities (OR = 2.3; 95% CI = 0.993 - 5.568; p = 0.04). In Buenaventura, the mortality rate was 5% compared to the 15% reported in the other municipalities. Treatment failures were not reported in Buenaventura, but 35% did not continue with the follow-up. Treatment success was higher in Buenaventura (56 %). Conclusion. A strengthened program in Buenaventura presented better programmatic results than those from the other municipalities of Valle del Cauca. Access to molecular tests, availability of shortened treatments, and continuous monitoring to identify adverse reactions to antituberculosis medications are routes for all other control programs.
Introducción. El manejo adecuado de la tuberculosis multirresistente es una estrategia priorizada para el control de la tuberculosis en el mundo. Objetivo. Evaluar las diferencias entre las características demográficas y clínicas, y los indicadores programáticos de los pacientes con diagnóstico confirmado de tuberculosis pulmonar resistente a rifampicina o multirresistente en Buenaventura, frente a la cohorte de los demás municipios del Valle del Cauca entre 2013 y 2016. Materiales y métodos. Se desarrolló un estudio analítico de cohortes para comparar los registros de pacientes mayores de 15 años con tuberculosis multirresistente, del Programa de Tuberculosis de Buenaventura (con ácido paraaminosalicílico), frente a los demás municipios del Valle del Cauca (sin ácido paraaminosalicílico). Resultados. Se registraron 99 casos con una mediana de edad de 40 años (RIC = 26- 53); en Buenaventura, el 56 % eran mujeres; en los demás municipios, predominaron los hombres (67 %); el 95 % de los evaluados tenía aseguramiento en salud. La comorbilidad más frecuente fue diabetes (14 %). Las reacciones adversas a medicamentos antituberculosos en Buenaventura fueron 1,3 veces más frecuentes que en los demás municipios (OR = 2,3; IC95 %: 0,993 - 5,568; p = 0,04). En Buenaventura falleció el 5 % de los casos frente al 15 % reportado en los demás municipios. No hubo fracasos con el tratamiento en Buenaventura, pero se reportó un 35 % de pérdida del seguimiento. El éxito del tratamiento fue mayor en Buenaventura en el 56 %. Conclusión. El programa fortalecido de Buenaventura presentó mejores resultados programáticos que los demás municipios del Valle del Cauca. El acceso a pruebas moleculares, la disponibilidad de tratamientos acortados y el seguimiento continuo para identificar reacciones adversas a medicamentos antituberculosos son un derrotero para todos los programas de control.
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Rifampin , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Colombia/epidemiología , Adulto , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Rifampin/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Antituberculosos/uso terapéutico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/epidemiología , Estudios de Cohortes , Ácido Aminosalicílico/uso terapéutico , Adulto Joven , Antibióticos Antituberculosos/uso terapéuticoRESUMEN
BACKGROUND: Continuous monitoring of antimicrobial resistance (AMR) in Uganda involves testing bacterial isolates from clinical samples at national and regional hospitals. Although the National Microbiology Reference Laboratory (NMRL) analyzes these isolates for official AMR surveillance data, there's limited integration into public health planning. To enhance the utilization of NMRL data to better inform drug selection and public health strategies in combating antibiotic resistance, we evaluated the trends and spatial distribution of AMR to common antibiotics used in Uganda. METHODS: We analyzed data from pathogenic bacterial isolates from blood, cerebrospinal, peritoneal, and pleural fluid from AMR surveillance data for 2018-2021. We calculated the proportions of isolates that were resistant to common antimicrobial classes. We used the chi-square test for trends to evaluate changes in AMR resistance over the study period. RESULTS: Out of 537 isolates with 15 pathogenic bacteria, 478 (89%) were from blood, 34 (6.3%) were from pleural fluid, 21 (4%) were from cerebrospinal fluid, and 4 (0.7%) were from peritoneal fluid. The most common pathogen was Staphylococcus aureus (20.1%), followed by Salmonella species (18.8%). The overall change in resistance over the four years was 63-84% for sulfonamides, fluoroquinolones macrolides (46-76%), phenicols (48-71%), penicillins (42-97%), ß-lactamase inhibitors (20-92%), aminoglycosides (17-53%), cephalosporins (8.3-90%), carbapenems (5.3-26%), and glycopeptides (0-20%). There was a fluctuation in resistance of Staphylococcus aureus to methicillin (60%-45%) (using cefoxitin resistance as a surrogate for oxacillin resistance) Among gram-negative organisms, there were increases in resistance to tetracycline (29-78% p < 0.001), ciprofloxacin (17-43%, p = 0.004), ceftriaxone (8-72%, p = 0.003), imipenem (6-26%, p = 0.004), and meropenem (7-18%, p = 0.03). CONCLUSION: The study highlights a concerning increase in antibiotic resistance rates over four years, with significant increase in resistance observed across different classes of antibiotics for both gram-positive and gram-negative organisms. This increased antibiotic resistance, particularly to commonly used antibiotics like ceftriaxone and ciprofloxacin, makes adhering to the WHO's Access, Watch, and Reserve (AWaRe) category even more critical. It also emphasizes how important it is to guard against the growing threat of antibiotic resistance by appropriately using medicines, especially those that are marked for "Watch" or "Reserve."
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Antibacterianos , Farmacorresistencia Bacteriana , Humanos , Uganda/epidemiología , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/tratamiento farmacológico , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/clasificación , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificaciónRESUMEN
Background: Staphylococcus aureus (S. aureus) infecting animals and humans via close contact, handling, or consuming contaminated products is a growing public health concern. In Ethiopia, it is important to examine the overall prevalence of S. aureus, patterns of multidrug resistance, and potential risks in human-animal interface settings. Thus, this review was conducted to estimate the pooled prevalence of S. aureus, its multidrug resistance, and potential risk factors for worker-animal-working equipment interactions. Methods: This systematic review and meta-analysis were carried out by the PRISMA guidelines. The research articles were searched from PubMed, HINARI, Web of Sciences, and Google Scholar databases. Results: This meta-analysis included 13 independent articles and 52 dependent studies. In total, 5,329 humans, 5,475 animals, and 5,119 samples of working equipment were analyzed. The pooled prevalence of S. aureus at the interfaces between humans, animals, and working equipment was 22%, there was a high level of heterogeneity (I2 = 94%: p < 0.01). The overall pooled prevalence of S. aureus in dairy farm sources was 23% (95% CI, 17-30%) compared to 18% in abattoirs. The pooled prevalence of S. aureus was estimated to be 25% for human sources, 23% for animal sources, and 19% for working equipment. The total multidrug resistance (MDR) rate was 27%. The present study illustrates that a predominant antimicrobials comprising ampicillin, penicillin, chloramphenicol, tetracycline, and ciprofloxacin, accounts for the development of resistance in S. aureus strains, with a prevalence of 72%. According to the qualitative assessment of potential risk factors, animal age, worker education, lactation stage, and hand washing by milkers influenced the circulation of S. aureus at animal-worker and working equipment interfaces. Conclusion: The pooled prevalence of S. aureus at the interface of human,-and animal-working equipment was quantified at 22%. S. aureus was found in humans, animals, and equipment at nearly the same rate. The results of this study demonstrate that S. aureus is hazardous and circulates among animals, workers, and equipment: farmers, animal owners, employees, and the public need to be educated about S. aureus. Moreover, animals and work equipment should be included in the control and prevention of S. aureus infection.
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Farmacorresistencia Bacteriana Múltiple , Infecciones Estafilocócicas , Staphylococcus aureus , Humanos , Animales , Etiopía/epidemiología , Factores de Riesgo , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/aislamiento & purificación , Prevalencia , Antibacterianos/farmacologíaRESUMEN
BACKGROUND: The 2016 IDSA guideline recommends a treatment duration of at least 7 days for hospital-acquired (HAP)/ventilator-associated pneumonia (VAP). The limited literature has demonstrated higher rates of recurrence for non-glucose fermenting gram-negative bacilli with short course therapy, raising the concern of optimal treatment duration for these pathogens. Therefore, we aimed to compare the outcomes for patients receiving shorter therapy treatment (≤ 8 days) versus longer regimen (> 8 days) for the treatment of multidrug resistant (MDR) Pseudomonas pneumonia. METHODS: A single-center, retrospective cohort study was conducted to evaluate adult patients receiving an antimicrobial regimen with activity against MDR Pseudomonas aeruginosa in respiratory culture between 2017 and 2020 for a minimum of 6 consecutive days. Exclusion criteria were inmates, those with polymicrobial pneumonia, community-acquired pneumonia, and infections requiring prolonged antibiotic therapy. RESULTS: Of 427 patients with MDR P. aeruginosa respiratory isolates, 85 patients were included. Baseline characteristics were similar among groups with a median age of 65.5 years and median APACHE 2 score of 20. Roughly 75% had ventilator-associated pneumonia. Compared to those who received ≤ 8 days of therapy, no difference was seen for clinical success in patients treated for more than 8 days (80% vs. 65.5%, p = 0.16). The number of 30-day and 90-day in-hospital mortality, 30-days relapse, and other secondary outcomes did not significantly differ among the treatment groups. CONCLUSIONS: Prolonging treatment duration beyond 8 days did not improve patient outcomes for MDR P. aeruginosa HAP/VAP.
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Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Humanos , Masculino , Femenino , Pseudomonas aeruginosa/efectos de los fármacos , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Anciano , Persona de Mediana Edad , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/mortalidad , Neumonía Asociada al Ventilador/tratamiento farmacológico , Neumonía Asociada al Ventilador/microbiología , Neumonía Asociada al Ventilador/mortalidad , Resultado del Tratamiento , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/mortalidad , Duración de la TerapiaRESUMEN
INTRODUCTION: Febrile neutropenia (FN) is one of the most common complications of stem cell transplantation. The aim of this analysis was to evaluate the frequency of sepsis in patients with FN colonized with resistant Gram negative bacteria (Extended spectrum ß-lactamase positive, multidrug resistant (MDR) P. aeruginosa) and the choice of primary antibiotic in colonized patients. PATIENTS AND METHODS: This was a retrospective study analyzed data from patients who underwent hematopoietic stem cell transplantation from 01/2018 to 09/2022. Data were extracted from the hospital information system. RESULTS: Carbapenem as the primary antibiotic of choice was chosen in 10.9% of non-colonized +/-AmpC patients, 31.5% of ESBL+ patients, and 0% of MDR P. aeruginosa patients. Patients with FN and MDR P. aeruginosa colonization had a high prevalence of sepsis (namely 100%, p = 0.0197). The spectrum of sepsis appeared to be different, with Gram negative bacilli predominating in the ESBL+ group (p = 0.0123, OR 5.39 [95% CI 1.55-18.76]). Colonizer sepsis was present in 100% of sepsis with MDR P. aeruginosa colonization (p=0.002), all in allogeneic transplantation (p=0.0003), with a mortality rate of 33.3% (p=0.0384). The incidence of sepsis in patients with ESBL+ colonization was 25.9% (p=0.0197), with colonizer sepsis in 50% of sepsis cases (p=0.0002), most in allogeneic transplantation (p=0.0003). CONCLUSION: The results show a significant risk of sepsis in FN with MDR P. aeruginosa colonization, this state is almost exclusively caused by the colonizer. At the same time, a higher risk of Gram negative sepsis has been demonstrated in patients colonized with ESBL+ bacteria.
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BACKGROUND: Tuberculosis (TB) is an airborne disease caused by Mycobacterium tuberculosis (M. tuberculosis). The world is currently facing challenges due to the spread of anti-tuberculosis drug-resistant of M. tuberculosis. Isoniazid-resistant (INH), is one of the first-line anti-tuberculosis agents that has a high resistance case. This study used Multiplex allele-specific Polymerase Chain Reaction (MAS-PCR) to detect the most common mutations associated with isoniazid resistance on inhA, katG, and ahpC gene. METHODS: This study used samples from clinical isolates of M. tuberculosis which had been tested for their antibiotic sensitivity of first-line anti-tuberculosis drugs. The DNA extraction process was carried out using the boiling method and then amplified with specific primers for inhA, katG, and ahpC genes using the MAS-PCR method. The results are then read on the electrophoretic gel with an interpretation of the mutation gene when the target gene DNA bands were absent according to the allele-specific fragments target. RESULTS: A total of 200 isolates were tested in this study consisting of isoniazid-resistant and susceptible with the largest distribution of Multi-Drug Resistant (MDR) isolates with a total of 146 isolates (73%). The most significant gene mutation was on the ahpC gene in 61 isolates (30,5%) and the combination mutation of the katG + ahpC gene in 52 isolates (26%) with sensitivity and specificity of the test reaching 87% and 42% for the detection of INH-resistant. CONCLUSION: Mutation on the ahpC gene has the highest percentage in this study. AhpC gene can be considered one of the essential genes to be tested for the cause of isoniazid-resistant. Using MAS-PCR for detecting gene mutation in isoniazid-resistant was simple and easy, it has the potential to be widely used as a rapid screening molecular test.
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Antituberculosos , Proteínas Bacterianas , Catalasa , Isoniazida , Mutación , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Indonesia , Isoniazida/farmacología , Isoniazida/uso terapéutico , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Proteínas Bacterianas/genética , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Catalasa/genética , Oxidorreductasas/genética , Pruebas de Sensibilidad Microbiana , Femenino , Masculino , Adulto , Reacción en Cadena de la Polimerasa Multiplex , Farmacorresistencia Bacteriana Múltiple/genéticaRESUMEN
Enteropathogenic Escherichia coli (EPEC) are pathogens associated with gastrointestinal illnesses. Dogs and cats can harbor EPEC, and antimicrobial resistance may impair necessary treatments. This study characterized E. coli strains from dogs and cats, focusing on phylogroup classification, virulence factors, and antimicrobial resistance profiles. Ninety-seven E. coli isolates from fecal samples of 31 dogs and 3 cats were obtained from a private diagnostic laboratory in Botucatu, Brazil, from March to October 2021. The antimicrobial susceptibility was assessed using the disk diffusion method. Polymerase chain reaction (PCR) was employed to screen for blaCTX-M and genes encoding virulence factors, as well as to classify the isolates into phylogroups. Twenty isolates were positive for intimin encoding gene eae and, consequently, these isolates were classified as EPEC (20.62%). Notably, 5.1% (5/97) of the isolates exhibited extended-spectrum ß-lactamase (ESBL) production and 13.4% (13/97) were identified as multidrug-resistant bacteria. Phylogroups A and B2 were the most prevalent, comprising 29.9% (29/97) and 26.8% (26/97) of the bacterial isolates, respectively. This characterization highlights the prevalence of EPEC in domestic animals, emphasizing the potential risk they pose to public health and highlighting the urgency of responsible antimicrobial use in veterinary practices and the important role of laboratories in the surveillance of pathogenic multidrug-resistant bacteria.
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Antimicrobial resistance poses an escalating threat to human health, necessitating the development of novel antimicrobial agents capable of addressing challenges posed by antibiotic-resistant bacteria. Thanatin, a 21-amino acid ß-hairpin insect antimicrobial peptide featuring a single disulfide bond, exhibits broad-spectrum antibacterial activity, particularly effective against multidrug-resistant strains. The outer membrane biosynthesis system is recognized as a critical vulnerability in antibiotic-resistant bacteria, which thanatin targets to exert its antimicrobial effects. This peptide holds significant promise for diverse applications. This review begins with an examination of the structure-activity relationship and synthesis methods of thanatin. Subsequently, it explores thanatin's antimicrobial activity, detailing its various mechanisms of action. Finally, it discusses prospective clinical, environmental, food, and agricultural applications of thanatin, offering valuable insights for future research endeavors.
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Péptidos Catiónicos Antimicrobianos , Farmacorresistencia Bacteriana Múltiple , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Humanos , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/química , Antibacterianos/farmacología , Antibacterianos/química , Relación Estructura-Actividad , Animales , Bacterias/efectos de los fármacos , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: The dwindling antibiotic reserve owing to augmented drug-resistant bacteria is a major handicap for treating physicians. Klebsiella pneumoniae, a gram-negative encapsulated member of the Enterobacteriaceae family, is one such pathogenic bacteria. Carbapenemase-producing Klebsiella pneumoniae is globally recognized as one of the most critical bacterial threats to public health due to its extremely limited treatment options. Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections pose therapeutic challenges due to simultaneous resistance to various other groups of antibiotics. In this study, we have evaluated the synergistic effect of fosfomycinagainst CRKP isolates when used in combination with colistin by applying the Checkerboard method. METHODS: A laboratory-based prospective study was conducted in the Department of Microbiology, JSS Hospital, Mysuru, for a period of one year after obtaining ethical clearance. Klebsiella pneumoniae isolates obtained from clinical samples were screened for carbapenem resistance by the VITEK-2 compact system (bioMérieux, Marcy-l'Étoile, France). The minimum inhibitory concentration (MIC) of colistin and fosfomycin was individually ascertained by broth microdilution (BMD). Finally, the synergistic activity of the fosfomycin-colistin combination was determined by the BMD-based Checkerboard method. RESULTS: Among the 50 CRKP isolates, 36 (72%) isolates showed synergism, eight (16%) isolates showed indifference and six (12%) isolates showed partial synergism, while none of them showed additivity and antagonism by the Checkerboard method. These results are found to be statistically significant (chi-square value of 116.204 and p-value of < 0.00001). CONCLUSION: This study showed a promising in-vitro synergy between the drugs fosfomycin and colistin by Checkerboard BMD testing protocol. Colistin being a reserve antibiotic, monotherapy comes with the limitations of higher chances of resistance as well as toxicity, which can be overcome by combination therapy, thereby decreasing CRKP-associated mortality rates and delivering holistic patient benefit.