RESUMEN

OBJECTIVE: Thymidine-dependent small-colony variants (TD-SCVs) of Staphylococcus aureus are being isolated with increasing frequency from patients with cystic fibrosis (CF). The aim of this study was to evaluate the relationship between TD-SCV isolation and pulmonary function in patients with CF, as well as to determine whether the emergence of TD-SCVs was associated with trimethoprim-sulfamethoxazole (TMP-SMX) use and with coinfection with other microorganisms. METHODS: This was a retrospective case-control study including patients with CF who visited the Clinical Hospital Complex of the Federal University of Paraná, in Curitiba, Brazil, between 2013 and 2022. Demographic, clinical, and spirometric data, as well as information on TD-SCVs and other isolated microorganisms, were collected from the medical records of patients with CF and TD-SCVs (TD-SCV group; n = 32) and compared with those of a matched group of patients with CF without TD-SCVs (control group; n = 64). RESULTS: Isolation of TD-SCVs was positively associated with TMP-SMX use (p = 0.009), hospitalization (p < 0.001), and impaired pulmonary function (p = 0.04). CONCLUSIONS: The use of TMP-SMX seems to contribute to the emergence of TD-SCVs, the isolation of which was directly associated with worse pulmonary function in our sample.

Asunto(s)

Fibrosis Quística , Infecciones Estafilocócicas , Staphylococcus aureus , Humanos , Fibrosis Quística/microbiología , Fibrosis Quística/fisiopatología , Estudios Retrospectivos , Masculino , Femenino , Estudios de Casos y Controles , Staphylococcus aureus/efectos de los fármacos , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/fisiopatología , Adulto , Adulto Joven , Adolescente , Timidina/análogos & derivados , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol/farmacología , Pulmón/fisiopatología , Pulmón/microbiología , Pulmón/efectos de los fármacos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Niño , Brasil , Pruebas de Función Respiratoria

RESUMEN

Background: Biofilm production in nonfermenting Gram-negative bacteria influences drug resistance. The aim of this work was to evaluate the effect of different antibiotics on biofilm eradication of clinical isolates of Achromobacter, Burkholderia, and Stenotrophomonas maltophilia. Methods: Clinical isolates were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry in a third-level hospital in Monterrey, Mexico. Crystal violet staining was used to determine biofilm production. Drug susceptibility testing was determined by broth microdilution in planktonic cells and biofilm cells. Results: Resistance in planktonic cells was moderate to trimethoprim-sulfamethoxazole, and low to chloramphenicol, minocycline, levofloxacin (S. maltophilia and Burkholderia), ceftazidime, and meropenem (Burkholderia and Achromobacter). Biofilm eradication required higher drug concentrations of ceftazidime, chloramphenicol, levofloxacin, and trimethoprim-sulfamethoxazole than planktonic cells (p < 0.05). Levofloxacin showed biofilm eradication activity in S. maltophilia, minocycline and meropenem in Burkholderia, and meropenem in Achromobacter. Conclusions: Drug resistance increased due to biofilm production for some antibiotics, particularly ceftazidime and trimethoprim-sulfamethoxazole for all three pathogens, chloramphenicol for S. maltophilia and Burkholderia, and levofloxacin for Burkholderia. Some antibiotics could be used for the treatment of biofilm-associated infections in our population, such as levofloxacin for S. maltophilia, minocycline and meropenem for Burkholderia, and meropenem for Achromobacter.

Asunto(s)

Achromobacter , Antibacterianos , Biopelículas , Burkholderia , Infecciones por Bacterias Gramnegativas , Pruebas de Sensibilidad Microbiana , Stenotrophomonas maltophilia , Biopelículas/efectos de los fármacos , Stenotrophomonas maltophilia/efectos de los fármacos , Antibacterianos/farmacología , Humanos , Burkholderia/efectos de los fármacos , Achromobacter/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Farmacorresistencia Bacteriana , Combinación Trimetoprim y Sulfametoxazol/farmacología , México , Ceftazidima/farmacología , Plancton/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple , Levofloxacino/farmacología

RESUMEN

Antibiotic exposure is associated with resistant bacterial colonization, but this relationship can be obscured in community settings owing to horizontal bacterial transmission and broad distributions. Locality-level exposure estimates considering inhabitants' length of stay, exposure history, and exposure conditions of areas nearby could clarify these relationships. We used prescription data filled during 2010-2015 for 23 antibiotic types for members of georeferenced households in a population-based infectious disease surveillance platform. For each antibiotic and locality, we generated exposure estimates, expressed in defined daily doses (DDD) per 1000 inhabitant days of observation (IDO). We also estimated relevant environmental parameters, such as the distance of each locality to water, sanitation, and other amenities. We used data on ampicillin, ceftazidime, and trimethoprim-and-sulfamethoxazole resistant Escherichia coli colonization from stool cultures of asymptomatic individuals in randomly selected households. We tested exposure-colonization associations using permutation analysis of variance and logistic generalized linear mixed-effect models. Overall, exposure was highest for trimethoprim-sulfamethoxazole (1.8 DDD per 1000 IDO), followed by amoxicillin (0.7 DDD per 1000 IDO). Of 1,386 unique household samples from 195 locations tested between September 2015 and January 2016, 90%, 85% and 4% were colonized with E. coli resistant to trimethoprim and sulfamethoxazole, ampicillin, and ceftazidime, respectively. Ceftazidime-resistant E. coli colonization was common in areas with increased trimethoprim-sulfamethoxazole, cloxacillin, and erythromycin exposure. No association with any of the physical environmental variables was observed. We did not detect relationships between distribution patterns of ampicillin or trimethoprim-and-sulfamethoxazole resistant E. coli colonization and the risk factors assessed. Appropriate temporal and spatial scaling of raw antibiotic exposure data to account for evolution and ecological contexts of antibiotic resistance could clarify exposure-colonization relationships in community settings and inform community stewardship program.

Asunto(s)

Antibacterianos , Infecciones por Escherichia coli , Escherichia coli , Humanos , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Antibacterianos/farmacología , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/tratamiento farmacológico , Femenino , Masculino , Adulto , Niño , Adolescente , Preescolar , Persona de Mediana Edad , Combinación Trimetoprim y Sulfametoxazol/farmacología , Ceftazidima/farmacología , Farmacorresistencia Bacteriana/efectos de los fármacos , Adulto Joven , Ampicilina/farmacología , Lactante

RESUMEN

Antimicrobial resistance (AMR) in the community is increasing worldwide. We aimed to assess AMR trends in Escherichia coli from the community urine isolates in French Amazonia. We conducted a retrospective study from January 2016 to December 2022 in the Cayenne General Hospital microbiology laboratory (French Guiana). It included all urine samples positive for E. coli collected from adult outpatients. During the study period, 3,443 urinalyses positive for E. coli were studied. In 46% of cases, patients were women. In 64.4% of cases, E. coli were ß-lactamase producers. The most frequently diagnosed resistance mechanisms were penicillinase production and sparing third-generation cephalosporins. Isolated E. coli were extended-spectrum ß-lactamase (ESBL) producers in 6.1% of cases. Overall, E. coli was susceptible to amoxicillin in 35.9% [95% CI: 34.3-37.5], to amoxicillin/clavulanic acid in 62.2% [95% CI: 60.6-63.9], to cefotaxime in 94% [95% CI: 93.1-94.7], to gentamicin in 92.1% [95% CI: 89.1-92.6], to ofloxacin in 76.8% [95% CI: 75.3-78.2], to trimethoprim/sulfamethoxazole (SXT) in 58.8% [95% CI: 57.1-60.5], to fosfomycin in 99.1% [95% CI: 98.6-99.4], and to nitrofurantoin in 99% of cases [95% CI: 98.6-99.3]. We have observed a gradual decline in the susceptibility profile of E. coli for amoxicillin/clavulanic acid (P <0.001), piperacillin/tazobactam (P = 0.003), and temocillin (P = 0.006). However, susceptibility to ciprofloxacin was increasing (P = 0.001). In contrast, the susceptibility trends for amoxicillin, third-generation cephalosporins, gentamicin, SXT, nitrofurantoin, and fosfomycin remained stable over the 28 quarters of the study. In conclusion, isolated E. coli from outpatient urinalyses showed increased resistance profiles involving penicillinase and ESBL production. Close monitoring and strategies to decrease antibiotic consumption in the community are needed.

Asunto(s)

Antibacterianos , Infecciones por Escherichia coli , Escherichia coli , Pruebas de Sensibilidad Microbiana , Pacientes Ambulatorios , Humanos , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Femenino , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/orina , Masculino , Estudios Retrospectivos , Guyana Francesa/epidemiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Pacientes Ambulatorios/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Prevalencia , Infecciones Urinarias/microbiología , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/epidemiología , beta-Lactamasas/genética , Farmacorresistencia Bacteriana , Anciano , Combinación Trimetoprim y Sulfametoxazol/farmacología , Adulto Joven

RESUMEN

OBJECTIVES: The World Health Organization named Stenotrophomonas maltophilia (SM) a critical multi-drug resistant threat, necessitating rapid diagnostic strategies. Traditional culturing methods require up to 96 h, including 72 h for bacterial growth, identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) through protein profile analysis, and 24 h for antibiotic susceptibility testing. In this study, we aimed at developing an artificial intelligence-clinical decision support system (AI-CDSS) by integrating MALDI-TOF MS and machine learning to quickly identify levofloxacin and trimethoprim/sulfamethoxazole resistance in SM, optimizing treatment decisions. METHODS: We selected 8,662 SM from 165,299 MALDI-TOF MS-analysed bacterial specimens, collected from a major medical centre and four secondary hospitals. We exported mass-to-charge values and intensity spectral profiles from MALDI-TOF MS .mzML files to predict antibiotic susceptibility testing results, obtained with the VITEK-2 system using machine learning algorithms. We optimized the models with GridSearchCV and 5-fold cross-validation. RESULTS: We identified distinct spectral differences between resistant and susceptible SM strains, demonstrating crucial resistance features. The machine learning models, including random forest, light-gradient boosting machine, and XGBoost, exhibited high accuracy. We established an AI-CDSS to offer healthcare professionals swift, data-driven advice on antibiotic use. CONCLUSIONS: MALDI-TOF MS and machine learning integration into an AI-CDSS significantly improved rapid SM resistance detection. This system reduced the identification time of resistant strains from 24 h to minutes after MALDI-TOF MS identification, providing timely and data-driven guidance. Combining MALDI-TOF MS with machine learning could enhance clinical decision-making and improve SM infection treatment outcomes.

Asunto(s)

Antibacterianos , Inteligencia Artificial , Farmacorresistencia Bacteriana Múltiple , Infecciones por Bacterias Gramnegativas , Aprendizaje Automático , Pruebas de Sensibilidad Microbiana , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Stenotrophomonas maltophilia , Combinación Trimetoprim y Sulfametoxazol , Stenotrophomonas maltophilia/efectos de los fármacos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Antibacterianos/farmacología , Humanos , Combinación Trimetoprim y Sulfametoxazol/farmacología , Sistemas de Apoyo a Decisiones Clínicas , Levofloxacino/farmacología

RESUMEN

BACKGROUND: Stenotrophomonas maltophilia is a carbapenem-resistant Gram-negative pathogen increasingly responsible for difficult-to-treat nosocomial infections. OBJECTIVES: To describe the contemporary clinical characteristics and genome epidemiology of patients colonized or infected by S. maltophilia in a multicentre, prospective cohort. METHODS: All patients with a clinical culture growing S. maltophilia were enrolled at six tertiary hospitals across Japan between April 2019 and March 2022. The clinical characteristics, outcomes, antimicrobial susceptibility and genomic epidemiology of cases with S. maltophilia were investigated. RESULTS: In total, 78 patients were included representing 34 infection and 44 colonization cases. The median age was 72.5 years (IQR, 61-78), and males accounted for 53 cases (68%). The most common comorbidity was localized solid malignancy (39%). Nearly half of the patients (44%) were immunosuppressed, with antineoplastic chemotherapy accounting for 31%. The respiratory tract was the most common site of colonization (86%), whereas bacteraemia accounted for most infection cases (56%). The 30 day all-cause mortality rate was 21%, which was significantly higher in infection cases than colonization cases (35% versus 9%; adjusted HR, 3.81; 95% CI, 1.22-11.96). Susceptibility rates to ceftazidime, levofloxacin, minocycline and sulfamethoxazole/trimethoprim were 14%, 65%, 87% and 100%, respectively. The percentage of infection ranged from 13% in the unclassified group to 86% in genomic group 6A. The percentage of non-susceptibility to ceftazidime ranged from 33% in genomic group C to 100% in genomic groups 6 and 7 and genomic group geniculate. CONCLUSIONS: In this contemporary multicentre cohort, S. maltophilia primarily colonized the respiratory tract, whereas patients with bacteraemia had the highest the mortality from this pathogen. Sulfamethoxazole/trimethoprim remained consistently active, but susceptibility to levofloxacin was relatively low. The proportions of cases representing infection and susceptibility to ceftazidime differed significantly based on genomic groups.

Asunto(s)

Antibacterianos , Infecciones por Bacterias Gramnegativas , Pruebas de Sensibilidad Microbiana , Stenotrophomonas maltophilia , Humanos , Stenotrophomonas maltophilia/genética , Stenotrophomonas maltophilia/efectos de los fármacos , Stenotrophomonas maltophilia/aislamiento & purificación , Stenotrophomonas maltophilia/clasificación , Masculino , Anciano , Japón/epidemiología , Femenino , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Persona de Mediana Edad , Estudios Prospectivos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infección Hospitalaria/microbiología , Infección Hospitalaria/epidemiología , Genoma Bacteriano , Bacteriemia/microbiología , Bacteriemia/epidemiología , Epidemiología Molecular , Combinación Trimetoprim y Sulfametoxazol/farmacología , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico

RESUMEN

Although recent propagation of carbapenemase-producing Enterobacterales (CPE) has become a problem worldwide, the picture of CPE infection in Japan has not fully been elucidated. In this study, we examined clinical and microbiological characteristics of invasive CPE infection occurring at 8 hospitals in Minami Ibaraki Area between July 2001 to June 2017. Of 7294 Enterobacterales strains isolated from independent cases of bacteremia and/or meningitis, 10 (0.14%) were CPE (8 Enterobacter cloacae-complex, 1 Escherichia coli, and 1 Edwardsiella tarda）, all of which had the blaIMP-1 gene and susceptible to gentamicin and trimethoprim/sulfamethoxazole. These strains were isolated from 7 adult and 2 infant bacteremia (1 infant patient developed CPE bacteremia twice) after 2007. The most common portal of entry was intravenous catheters. All of the adult patients were recovered, while the infant patients eventually died. Genomic analyses showed that the 8 E. cloacae-complex strains were classified into 5 groups, each of which was exclusively detected in specific facilities at intervals of up to 3 years, suggesting persistent colonization in the facilities. This study showed that invasive CPE infection in the area was rare, caused by IMP-1-type CPE having susceptibility to various antibiotics, and nonfatal among adult patients.

Asunto(s)

Antibacterianos , Bacteriemia , Proteínas Bacterianas , Infecciones por Enterobacteriaceae , Pruebas de Sensibilidad Microbiana , beta-Lactamasas , Humanos , Japón/epidemiología , Bacteriemia/microbiología , Bacteriemia/tratamiento farmacológico , Bacteriemia/epidemiología , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/tratamiento farmacológico , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Masculino , Femenino , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Lactante , Persona de Mediana Edad , Adulto , Anciano , Enterobacter cloacae/genética , Enterobacter cloacae/efectos de los fármacos , Enterobacter cloacae/aislamiento & purificación , Gentamicinas/farmacología , Gentamicinas/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol/farmacología , Anciano de 80 o más Años , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación

RESUMEN

BACKGROUND: Long-term treatment with trimethoprim-sulfamethoxazole (SXT) can lead to the formation of small-colony variants (SCVs) of Staphylococcus aureus. However, the mechanism behind SCVs formation remains poorly understood. In this study, we explored the phenotype and omics-based characterization of S. aureus SCVs induced by SXT and shed light on the potential causes of SCV formation. METHODS: Stable SCVs were obtained by continuously treating S. aureus isolates using 12/238 µg/ml of SXT, characterized by growth kinetics, antibiotic susceptibility testing, and auxotrophism test. Subsequently, a pair of representative strains (SCV and its parental strain) were selected for genomic, transcriptomic and metabolomic analysis. RESULTS: Three stable S. aureus SCVs were successfully screened and proven to be homologous to their corresponding parental strains. Phenotypic tests showed that all SCVs were non-classical mechanisms associated with impaired utilization of menadione, heme and thymine, and exhibited slower growth and higher antibiotic minimum inhibitory concentrations (MICs), compared to their corresponding parental strains. Genomic data revealed 15 missense mutations in 13 genes in the representative SCV, which were involved in adhesion, intramolecular phosphate transfer on ribose, transport pathways, and phage-encoded proteins. The combination analysis of transcriptome and metabolome identified 35 overlapping pathways possible associated with the phenotype switching of S. aureus. These pathways mainly included changes in metabolism, such as purine metabolism, pyruvate metabolism, amino acid metabolism, and ABC transporters, which could play a crucial role in promoting SCVs development by affecting nucleic acid synthesis and energy metabolism in bacteria. CONCLUSION: This study provides profound insights into the causes of S. aureus SCV formation induced by SXT. The findings may offer valuable clues for developing new strategies to combat S. aureus SCV infections.

Asunto(s)

Antibacterianos , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus , Combinación Trimetoprim y Sulfametoxazol , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Perfilación de la Expresión Génica , Genómica , Metabolómica , Multiómica , Fenotipo , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Transcriptoma , Combinación Trimetoprim y Sulfametoxazol/farmacología

RESUMEN

The co-production of KPC and NDM carbapenemases in carbapenem-resistant Klebsiella pneumoniae (CRKP) complicates clinical treatment and increases mortality rates. The emergence of KPC-NDM CRKP is believed to result from the acquisition of an NDM plasmid by KPC CRKP, especially under the selective pressure of ceftazidime-avibactam (CZA). In this study, a CRKP-producing KPC-2 (JNP990) was isolated from a patient at a tertiary hospital in Shandong Province, China. Following sulfamethoxazole-trimethoprim (SXT) treatment, the isolate evolved into a strain that co-produces KPC and NDM (JNP989), accompanied by resistance to SXT (minimum inhibitory concentration >2/38 µg/mL) and CZA (dd ≤14 mm). Whole-genome sequencing and S1 nuclease pulsed-field gel electrophoresis revealed that JNP989 acquired an IncC plasmid (NDM plasmid) spanning 197 kb carrying sul1 and blaNDM-1 genes. The NDM plasmid could be transferred successfully into Escherichia coli J53 at a conjugation frequency of (8.70±2.47) × 10-4. The IncFⅡ/IncR plasmid carrying the blaKPC-2 gene in JNP990 could only be transferred in the presence of the NDM plasmid at a conjugation frequency of (1.93±0.41) × 10-5. Five CRKP strains with the same resistance pattern as JNP989, belonging to the same clone as JNP989, with sequence type 11 were isolated from other patients in the same hospital. Two strains lost resistance to CZA due to the loss of the blaNDM-1-carrying fragment mediated by insertion sequence 26. Plasmid stability testing indicated that the IncC plasmid was more stable than the blaNDM-1 genes in the hosts. This study describes the evolution of KPC-NDM CRKP and its spread in hospitalized patients following antibiotic treatment, highlighting the severity of the spread of resistance.

Asunto(s)

Antibacterianos , Brotes de Enfermedades , Infecciones por Klebsiella , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana , Plásmidos , Combinación Trimetoprim y Sulfametoxazol , beta-Lactamasas , Humanos , beta-Lactamasas/genética , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efectos de los fármacos , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/epidemiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol/farmacología , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Plásmidos/genética , China/epidemiología , Farmacorresistencia Bacteriana Múltiple/genética , Secuenciación Completa del Genoma , Combinación de Medicamentos , Ceftazidima/farmacología , Ceftazidima/uso terapéutico , Compuestos de Azabiciclo/farmacología , Compuestos de Azabiciclo/uso terapéutico , Proteínas Bacterianas/genética , Centros de Atención Terciaria

RESUMEN

Enterohemorrhagic Escherichia coli causes watery to bloody diarrhea, which may progress to hemorrhagic colitis and hemolytic-uremic syndrome. While early studies suggested that antibiotic treatment may worsen the pathology of an enterohemorrhagic Escherichia coli (EHEC) infection, recent work has shown that certain non-Shiga toxin-inducing antibiotics avert disease progression. Unfortunately, both intestinal bacterial infections and antibiotic treatment are associated with dysbiosis. This can alleviate colonization resistance, facilitate secondary infections, and potentially lead to more severe illness. To address the consequences in the context of an EHEC infection, we used the established mouse infection model organism Citrobacter rodentium ϕstx2dact and monitored changes in fecal microbiota composition during infection and antibiotic treatment. C. rodentium ϕstx2dact infection resulted in minor changes compared to antibiotic treatment. The infection caused clear alterations in the microbial community, leading mainly to a reduction of Muribaculaceae and a transient increase in Enterobacteriaceae distinct from Citrobacter. Antibiotic treatments of the infection resulted in marked and distinct variations in microbiota composition, diversity, and dispersion. Enrofloxacin and trimethoprim/sulfamethoxazole, which did not prevent Shiga toxin-mediated organ damage, had the least disruptive effects on the intestinal microbiota, while kanamycin and tetracycline, which rapidly cleared the infection without causing organ damage, caused a severe reduction in diversity. Kanamycin treatment resulted in the depletion of all but Bacteroidetes genera, whereas tetracycline effects on Clostridia were less severe. Together, these data highlight the need to address the impact of individual antibiotics in the clinical care of life-threatening infections and consider microbiota-regenerating therapies.IMPORTANCEUnderstanding the impact of antibiotic treatment on EHEC infections is crucial for appropriate clinical care. While discouraged by early studies, recent findings suggest certain antibiotics can impede disease progression. Here, we investigated the impact of individual antibiotics on the fecal microbiota in the context of an established EHEC mouse model using C. rodentium ϕstx2dact. The infection caused significant variations in the microbiota, leading to a transient increase in Enterobacteriaceae distinct from Citrobacter. However, these effects were minor compared to those observed for antibiotic treatments. Indeed, antibiotics that most efficiently cleared the infection also had the most detrimental effect on the fecal microbiota, causing a substantial reduction in microbial diversity. Conversely, antibiotics showing adverse effects or incomplete bacterial clearance had a reduced impact on microbiota composition and diversity. Taken together, our findings emphasize the delicate balance required to weigh the harmful effects of infection and antibiosis in treatment.

Asunto(s)

Antibacterianos , Citrobacter rodentium , Infecciones por Enterobacteriaceae , Heces , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Animales , Citrobacter rodentium/efectos de los fármacos , Ratones , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Heces/microbiología , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol/farmacología , Escherichia coli Enterohemorrágica/efectos de los fármacos , Enrofloxacina/farmacología , Enrofloxacina/uso terapéutico , Femenino , Modelos Animales de Enfermedad , Disbiosis/microbiología

RESUMEN

Pneumocystis jirovecii is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. People with HIV (PWH) who have low CD4 counts are one of the populations at the greatest risk of Pneumocystis jirovecii pneumonia (PCP). While guidelines have approached the diagnosis, prophylaxis, and management of PCP, the numerous studies of PCP in PWH are dominated by the 1980s and 1990s. As such, most studies have included younger male populations, despite PCP affecting both sexes and a broad age range. Many studies have been small and observational in nature, with an overall lack of randomized controlled trials. In many jurisdictions, and especially in low- and middle-income countries, the diagnosis can be challenging due to lack of access to advanced and/or invasive diagnostics. Worldwide, most patients will be treated with 21 days of high-dose trimethoprim sulfamethoxazole, although both the dose and the duration are primarily based on historical practice. Whether treatment with a lower dose is as effective and less toxic is gaining interest based on observational studies. Similarly, a 21-day tapering regimen of prednisone is used for patients with more severe disease, yet other doses, other steroids, or shorter durations of treatment with corticosteroids have not been evaluated. Now with the widespread availability of antiretroviral therapy, improved and less invasive PCP diagnostic techniques, and interest in novel treatment strategies, this review consolidates the scientific body of literature on the diagnosis and management of PCP in PWH, as well as identifies areas in need of more study and thoughtfully designed clinical trials.

Asunto(s)

Infecciones por VIH , Pneumocystis carinii , Neumonía por Pneumocystis , Femenino , Humanos , Masculino , Neumonía por Pneumocystis/diagnóstico , Neumonía por Pneumocystis/tratamiento farmacológico , Neumonía por Pneumocystis/prevención & control , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol/farmacología

RESUMEN

Stenotrophomonas maltophilia is a nonfermenting Gram-negative drug-resistant pathogen that causes healthcare-associated infections. Clinical isolates from Mexico were assessed for biofilm formation using crystal violet staining. Antimicrobial susceptibility was evaluated in planktonic and biofilm cells using the broth microdilution method. The effects of antibiotics on biofilms were visualized using fluorescence microscopy. Fifty isolates were included in this study, of which 14 (28%) were biofilm producers (9 [64%] from blood and 5 [36%] from respiratory samples). In planktonic cells 4/50 (8%) of isolates were resistant to levofloxacin (8.0%) and 22/50 (44%) were resistant to trimethoprim-sulfamethoxazole. All isolates were resistant to levofloxacin and trimethoprim-sulfamethoxazole in biofilm cells. Bacterial biofilms treated with different concentrations of both antibiotics were completely disrupted. In conclusion, S. maltophilia isolated from blood had higher biofilm production than those isolated from respiratory samples. Biofilm production was associated with increased antibiotic resistance. Antibiotic monotherapy might not be the best course of action for the treatment of S. maltophilia infections in Mexico, because it might cause biofilm production and antimicrobial resistance.

Asunto(s)

Antibacterianos , Biopelículas , Infecciones por Bacterias Gramnegativas , Levofloxacino , Pruebas de Sensibilidad Microbiana , Stenotrophomonas maltophilia , Combinación Trimetoprim y Sulfametoxazol , Stenotrophomonas maltophilia/efectos de los fármacos , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Combinación Trimetoprim y Sulfametoxazol/farmacología , Levofloxacino/farmacología , Humanos , Antibacterianos/farmacología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , México , Microscopía Fluorescente

RESUMEN

BACKGROUND: Risk factors for ciprofloxacin or MDR in primary care urine specimens are not well defined. OBJECTIVES: We created a primary care-specific antibiogram for Escherichia coli isolates from cases with complicated and uncomplicated urinary tract infection (UTI) and evaluated risk factors for ciprofloxacin, trimethoprim/sulfamethoxazole and MDR among Enterobacterales. METHODS: We conducted a cross-sectional study to determine resistance and risk factors by collecting urine cultures from all patients (≥18 years) presenting with provider-suspected UTI at two primary care, safety-net clinics in Houston, TX, USA between November 2018 and March 2020. RESULTS: Among 1262 cultures, 308 cultures grew 339 uropathogens. Patients with Enterobacterales (n = 199) were mostly female (93.5%) with a mean age of 48.5 years. E. coli was the predominant uropathogen isolated (n = 187/339; 55%) and had elevated trimethoprim/sulfamethoxazole (43.6%) and ciprofloxacin (29.5%) resistance, low nitrofurantoin (1.8%) resistance, and no fosfomycin resistance. Among E. coli, 10.6% were ESBL positive and 24.9% had MDR. Birth outside the U.S.A., prior (2 year) trimethoprim/sulfamethoxazole resistance, and diabetes mellitus were associated with trimethoprim/sulfamethoxazole resistance. Prior (60 day) fluoroquinolone use, prior ciprofloxacin resistance and both diabetes mellitus and hypertension were strongly associated with ciprofloxacin resistance. Prior fluoroquinolone use and a history of resistance to any studied antibiotic were associated with MDR, while pregnancy was protective. CONCLUSIONS: We found elevated resistance to UTI-relevant antimicrobials and novel factors associated with resistance; these data can be incorporated into clinical decision tools to improve organism and drug concordance.

Asunto(s)

Diabetes Mellitus , Gammaproteobacteria , Embarazo , Humanos , Femenino , Persona de Mediana Edad , Masculino , Ciprofloxacina/farmacología , Estudios Transversales , Escherichia coli , Combinación Trimetoprim y Sulfametoxazol/farmacología , Factores de Riesgo , Fluoroquinolonas , Pruebas de Sensibilidad Microbiana , Resistencia a Múltiples Medicamentos , Atención Primaria de Salud

RESUMEN

Antimicrobial resistance (AMR) trends in 114 generic Escherichia coli isolated from channel catfish and related fish species were investigated in this study. Of these, 45 isolates were from commercial-sized channel catfish harvested from fishponds in Alabama, while 69 isolates were from Siluriformes products, accessed from the U.S. Department of Agriculture Food Safety and Inspection Service' (FSIS) National Antimicrobial Resistance Monitoring System (NARMS) program. Antibiotic susceptibility testing and whole genome sequencing were performed using the GenomeTrakr protocol. Upon analysis, the fishpond isolates showed resistance to ampicillin (44%), meropenem (7%) and azithromycin (4%). The FSIS NARMS isolates showed resistance to tetracycline (31.9%), chloramphenicol (20.3%), sulfisoxazole (17.4%), ampicillin (5.8%) and trimethoprim-sulfamethoxazole, nalidixic acid, amoxicillin-clavulanic acid, azithromycin and cefoxitin below 5% each. There was no correlation between genotypic and phenotypic resistance in the fishpond isolates, however, there was in NARMS isolates for folate pathway antagonists: Sulfisoxazole vs. sul1 and sul2 (p = 0.0042 and p < 0.0001, respectively) and trimethoprim-sulfamethoxazole vs. dfrA16 and sul1 (p = 0.0290 and p = 0.013, respectively). Furthermore, correlations were found for tetracyclines: Tetracycline vs. tet(A) and tet(B) (p < 0.0001 each), macrolides: Azithromycin vs. mph(E) and msr(E) (p = 0.0145 each), phenicols: Chloramphenicol vs. mdtM (p < 0.0001), quinolones: Nalidixic acid vs. gyrA_S83L=POINT (p = 0.0004), and ß-lactams: Ampicillin vs. blaTEM-1 (p < 0.0001). Overall, we recorded differences in antimicrobial susceptibility testing profiles, phenotypic-genotypic concordance, and resistance to critically important antimicrobials, which may be a public health concern.

Asunto(s)

Escherichia coli , Ictaluridae , Animales , Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Azitromicina/farmacología , Tetraciclina/farmacología , Ácido Nalidíxico/farmacología , Combinación Trimetoprim y Sulfametoxazol/farmacología , Sulfisoxazol/farmacología , Pruebas de Sensibilidad Microbiana , Ampicilina/farmacología , Cloranfenicol

RESUMEN

Wild strains of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were tested in an experimental hyperbaric chamber to determine the possible effect of hyperbaric oxygen on the susceptibility of these strains to the antibiotics ampicillin, ampicillin + sulbactam, cefazolin, cefuroxime, cefoxitin, gentamicin, sulfamethoxazole + trimethoprim, colistin, oxolinic acid, ofloxacin, tetracycline, and aztreonam during their cultivation at 23 °C and 36.5 °C. Ninety-six-well inoculated microplates with tested antibiotics in Mueller-Hinton broth were cultured under standard incubator conditions (normobaric normoxia) for 24 h or in an experimental hyperbaric chamber (HAUX, Germany) for 24 h at 2.8 ATA of 100% oxygen (hyperbaric hyperoxia). The hyperbaric chamber was pressurised with pure oxygen (100%). Both cultures (normoxic and hyperoxic) were carried out at 23 °C and 36.5 °C to study the possible effect of the cultivation temperature. No significant differences were observed between 23 and 36.5 °C cultivation with or without the 2-h lag phase in Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Cultivation in a hyperbaric chamber at 23 °C and 36.5 °C with or without a 2-h lag phase did not produce significant changes in the minimum inhibitory concentration (MIC) of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. For the tested strains of Pseudomonas aeruginosa, the possible effect of hyperbaric oxygen on their antibiotic sensitivity could not be detected because the growth of these bacteria was completely inhibited by 100% hyperbaric oxygen at 2.8 ATA under all hyperbaric conditions tested at 23 °C and 36.5 °C. Subsequent tests with wild strains of pseudomonads, burkholderias, and stenotrophomonads not only confirmed the fact that these bacteria stop growing under hyperbaric conditions at a pressure of 2.8 ATA of 100% oxygen but also indicated that inhibition of growth of these bacteria under hyperbaric conditions is reversible.

Asunto(s)

Oxigenoterapia Hiperbárica , Infecciones por Pseudomonas , Humanos , Antibacterianos/farmacología , Bacterias Anaerobias , Oxígeno , Bacterias , Pseudomonas aeruginosa , Ampicilina/farmacología , Escherichia coli , Combinación Trimetoprim y Sulfametoxazol/farmacología , Klebsiella pneumoniae , Estrés Oxidativo , Pruebas de Sensibilidad Microbiana , Sulbactam

RESUMEN

Urinary tract infection (UTI) caused by Escherichia coli is a significant health issue in children. Today especially E.coli O25b/ST131, defined as a pandemic clone, is a serious public health problem due to its high virulence and antimicrobial resistance rates. In this study, a total of 200 (100 first and 100 recurrent UTI-causing) E.coli isolates from urine samples sent to the Ankara University School of Medicine Cebeci Training and Research Hospital Central Laboratory between January and September 2021 with the preliminary diagnosis of UTI in pediatric patients aged three to 18 years were analyzed for antimicrobial resistance rates, phylogenetic group distributions, virulence factor frequencies and whether they belong to the O25b/ST131 clone. It is aimed in this study that, the obtained data will shed light on new studies for diagnosis, treatment and prophylaxis options that can be developed for more effective UTI management by contributing to the surveillance studies in our country. Antimicrobial susceptibility of E.coli isolates identified by conventional methods was evaluated by Kirby-Bauer disc diffusion method and extended spectrum beta-lactamase (ESBL) production was evaluated by double disc synergy test. Polymerase chain reaction (PCR) was used for the investigation of phylogenetic grouping, the O25b/ST131 clone, virulence genes and the molecular level classification of the isolates detected as uropathogenic E.coli (UPEC). Pulsed-field gel electrophoresis (PFGE) was performed with the isolates collected at different times from the same patient. The highest antimicrobial resistance rates observed were against ampicillin (n= 100, 50%), cefazolin (n= 99, 49.5%), trimethoprim-sulfamethoxazole (n= 55, 27.5%), amoxicillin-clavulanic acid (n= 43, 21.5%) and cefotaxime (n= 43, 21.5%). In recurrent UTI agents, resistance rates were higher for cefotaxime (n= 29, 29%), trimethoprim-sulfamethoxazole (n= 35, 35%) and cefepime (n= 25, 25%) and in O25b/ST131 isolates (n= 67) the rates were higher for amikacin (n= 3, 4.5%), gentamicin (n= 10, 14.9%) and ciprofloxacin (n= 17, 25.4%) when compared to the first UTI agents and non-O25b/ ST131 isolates (p< 0.05). It was found that 29% (n = 58) of the isolates were multidrug resistant (MDR) and 19% (n = 38) produced ESBL.The rate of recurrent UTI agents was found to be higher among ESBL producing isolates and/or MDR isolates (n= 36, 62% and n= 27, 71%, respectively, p< 0.05). It was found that 45.5% (n= 91) of the isolates were in D, 37.5% (n= 75) in B2, 12.5% (n= 25) in A, and 4.5% (n= 9) in B1 phylogenetic groups and isolates belonging to B2 and D phylogenetic groups had higher antibiotic resistance rates and carried more virulence genes (p< 0.05). Of the isolates, 33.5% (n= 67) were found to belong to the O25b/ST131 clone, no significant difference was found between the O25b/ST131 rates among the first and recurrent UTI agents (p> 0.05). It was determined that the isolates most frequently carry virulence genes for adhesion [fimH 97% (n= 194), papA 57% (n= 114), yfcV 49.5% (n= 99)] and iron uptake systems [fyuA 85.5% (n= 171), chuA 78% (n= 156), iutA 73% (n= 146)]. All virulence factors were detected more frequently in isolates belonging to the O25b/ST131 clone (p< 0.05). Of the isolates, 97% (n= 65) belonging to the O25b/ST131 clone and 27.1% (n= 36) not belonging to this clone were defined as UPEC with molecular analysis (p< 0.0001). Thirty-three isolates belonging to 15 patients were evaluated with PFGE, and it was observed that the latter isolate and the first isolate of eight patients (53%) had the same band profile. Focusing on surveillance, diagnostic testing, treatment algorithms, and preventive measures for E.coli and especially for ST131 clone, which is frequently observed as causative agent in childhood UTIs, will help to manage challenging E.coli infections.

Asunto(s)

Antiinfecciosos , Infecciones por Escherichia coli , Infecciones Urinarias , Humanos , Niño , Escherichia coli/genética , Filogenia , Factores de Virulencia/genética , Combinación Trimetoprim y Sulfametoxazol/farmacología , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/epidemiología , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/epidemiología , Infecciones Urinarias/diagnóstico , Cefotaxima/farmacología , beta-Lactamasas/genética , Células Clonales , Antiinfecciosos/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico

RESUMEN

Stenotrophomonas maltophilia is an emerging multidrug-resistant organism with an increasing frequency of hospital-acquired infections predominantly in developing countries. The purpose of this study was to determine the antibiotic resistance and frequency of the smeD, class 1 integron, and sul1 genes in clinical isolates of S. maltophilia in two Iranian provinces. From January 2020 to September 2021, 38 clinical isolates of S. maltophilia were collected from patients in hospitals in Tabriz and Sanandaj provinces of Iran. S. maltophilia isolates were confirmed by standard bacteriological tests and 16S rRNA gene PCR. Disk diffusion and the MIC test strip methods were used to determine the antibiotic resistance patterns. PCR was performed to investigate the presence of smeD, class 1 integron, and sul1 genes. The antimicrobial test for the isolated S. maltophilia showed a high level of sensitivity against most of the antibiotics used. Maximum sensitivity was recorded for ciprofloxacin (100% (38/38)) and levofloxacin 100% (38/38), followed by ceftazidime (97.36% (37/38)), trimethoprim-sulfamethoxazole (81.57% (31/38)), ticarcillin-clavulanate (60.52% (23/38)), and piperacillin-tazobactam (55.26% (21/38)). We observed a high prevalence of smeD (100% (38/38)) and class 1 integron (94.73% (36/38)) genes in the isolates, and none of the isolates carried the sul1 gene. The findings from this study indicate that resistance to trimethoprim-sulfamethoxazole was not observed, and still, trimethoprim-sulfamethoxazole is the best drug with desirable antimicrobial effect in the treatment of nosocomial infections caused by S. maltophilia strains. Despite the observation of a high number of class 1 integron, the sul1 gene was not observed, which indicates the role of this gene in high-level trimethoprim-sulfamethoxazole resistance and not having a role in low-level resistance. Based on our results, clinical microbiology laboratories need continuous surveillance of resistance rates to trimethoprim-sulfamethoxazole, because of the possibility of S. maltophilia acquiring trimethoprim-sulfamethoxazole-resistance by mobile gen elements.

Asunto(s)

Antiinfecciosos , Infección Hospitalaria , Stenotrophomonas maltophilia , Humanos , Stenotrophomonas maltophilia/genética , Integrones/genética , Irán , ARN Ribosómico 16S , Farmacorresistencia Bacteriana/genética , Antibacterianos/farmacología , Combinación Trimetoprim y Sulfametoxazol/farmacología , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Antiinfecciosos/farmacología , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología

RESUMEN

While trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line therapy of Stenotrophomonas maltophilia infections, colistin is one of the therapeutic options in cases of allergy or resistance to TMP-SMX. However, understanding the global status of resistance to colistin amongst S. maltophilia isolates could be helpful for appropriate antibiotic prescription. This study aimed to conduct a systematic review and meta-analysis to examine the prevalence of colistin resistance in clinical S. maltophilia isolates worldwide. According to eligibility criteria, a total of 61 studies were included in the analysis. The pooled prevalence for colistin resistance was 42% (95% CI: 35-49%), ranging from 0.1 to 97%. Subgroups analysis indicated that, the pooled prevalence of colistin resistance was 44% (95% CI: 29-60%) in 15 studies during 2000-2010, and it was estimated to be 41% (95% CI: 33-50%) in 46 articles from 2011 to 2021. It was 46% (95% CI: 35-58%) in the studies that used broth microdilution method, and 39% (95% CI: 30-49%) in the studies with other used methods. The resistance rate in Asian countries was 45% (95% CI: 31-60%), in European countries was 45% (95% CI: 34-56%) and in the countries of North and South America was 33% (95% CI: 20-46%). Our review showed notable resistance to colistin in clinical S. maltophilia isolates. Given the estimated resistance rates, alternative antibiotics could be preferred to treat serious infections due to S. maltophilia.

Asunto(s)

Infecciones por Bacterias Gramnegativas , Stenotrophomonas maltophilia , Humanos , Colistina/farmacología , Combinación Trimetoprim y Sulfametoxazol/farmacología , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Prevalencia , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/epidemiología , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico

RESUMEN

BACKGROUND: The 2011 Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases guidelines recommend ciprofloxacin or sulfamethoxazole-trimethoprim (SMX-TMP) as first-line agents to treat uncomplicated acute pyelonephritis (APN). OBJECTIVE: With increasing antimicrobial resistance rates and recent changes in practice patterns, the objective of this systematic review was to describe the effectiveness of cephalosporins for uncomplicated APN in more recently published literature. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used for reporting. We searched PubMed, Embase, and Scopus for publications between January 2010 and September 2022. Eligible articles detailed patients with uncomplicated APN, treated with first- to fourth-generation cephalosporins, and identified a clinical, microbiological, or health care utilization outcome. Studies with more than 30% of complicated APN patients, non-English-language studies, case reports, case series, pharmacodynamic or pharmacokinetic studies, and in vitro laboratory or animal studies were excluded. Screening, review, and extraction were performed independently by 2 researchers, plus a third for conflict resolution. Critical appraisal of studies was performed using Joanna Briggs Institute checklists. RESULTS: Eight studies met inclusion, including 5 cohort studies (62.5%), 2 randomized controlled trials (25%), and 1 nonrandomized experimental study (12.5%). Cephalosporins most used across the studies included cefazolin, cephalexin, cefuroxime, cefotaxime, cefdinir, cefditoren, and ceftriaxone. Outcomes assessed were diverse, including clinical or microbiological success and time to defervescence or symptom resolution. Cephalosporins displayed effectiveness for the treatment of acute uncomplicated APN regardless of study design or the presence of a comparison group. No trials reported inferiority of clinical treatment outcomes compared with a fluoroquinolone or SMX-TMP. CONCLUSION: Cephalosporins may be viable treatment options for the management of uncomplicated APN.

Asunto(s)

Enfermedades Transmisibles , Pielonefritis , Humanos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Cefalosporinas/uso terapéutico , Enfermedades Transmisibles/tratamiento farmacológico , Pielonefritis/tratamiento farmacológico , Pielonefritis/microbiología , Combinación Trimetoprim y Sulfametoxazol/farmacología , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico

RESUMEN

BACKGROUND: Non-typeable Haemophilus influenzae (NTHi) has become the major cause of invasive H. influenzae diseases in the post-H. influenzae type b vaccine era. The emergence of multidrug-resistant (MDR) NTHi is a growing public health problem. Herein, we investigated the molecular basis of MDR in NTHi. The isolated NTHi were subjected to antimicrobial susceptibility testing for 12 agents. Whole genome and plasmid sequencing were conducted and analyzed to identify significant genetic variations and plasmid-encoded genes conferred antibiotic resistance. RESULTS: Thirteen (50%) MDR NTHi isolates were obtained; of these, 92.3% were non-susceptible to ampicillin, 30.8% to amoxicillin-clavulanate, 61.5% to cefuroxime, 61.5% to ciprofloxacin/levofloxacin, 92.3% to trimethoprim-sulfamethoxazole, 30.8% to tetracycline, and 7.7% to azithromycin. Eight ampicillin-resistant isolates were ß-lactamase positive; of these, 6 carried blaTEM-1 and 2 carried blaROB-1, whereas 4 were ß-lactamase negative. Genetic variations in mrdA, mepA, and pbpG were correlated with amoxicillin-clavulanate non-susceptibility, whereas variations in ftsI and lpoA conferred cefuroxime resistance. Five variations in gyrA, 2 in gyrB, 3 in parC, 1 in parE, and 1 in the parC-parE intergenic region were associated with levofloxacin/ciprofloxacin non-susceptibility. Among these genes, 8 variations were linked to high-level levofloxacin resistance. Six variations in folA were associated with trimethoprim-sulfamethoxazole resistance. Plasmid-bearing tet(B) and mef(A) genes were responsible for tetracycline and azithromycin resistance in 4 and 1 MDR isolates, respectively. CONCLUSIONS: This study clarified the molecular epidemiology of MDR in NTHi. This can benefit the monitoring of drug resistance trends in NTHi and the adequate medical management of patients with NTHi infection.

Asunto(s)

Infecciones por Haemophilus , Haemophilus influenzae , Humanos , Haemophilus influenzae/genética , Cefuroxima/farmacología , Levofloxacino/farmacología , Combinación Trimetoprim y Sulfametoxazol/farmacología , Azitromicina , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Ampicilina , Infecciones por Haemophilus/tratamiento farmacológico , Combinación Amoxicilina-Clavulanato de Potasio , Tetraciclina , Ciprofloxacina , beta-Lactamasas/genética