Secondary infections in a cohort of patients with COVID-19 admitted to an intensive care unit: impact of gram-negative bacterial resistance

ABSTRACT Some studies have shown that secondary infections during the COVID-19 pandemic may have contributed to the high mortality. Our objective was to identify the frequency, types and etiology of bacterial infections in patients with COVID-19 admitted to an intensive care unit (ICU) and to evaluate the results of ICU stay, duration of mechanical ventilation (MV) and in-hospital mortality. It was a single-center study with a retrospective cohort of patients admitted consecutively to the ICU for more than 48 h between March and May 2020. Comparisons of groups with and without ICU- acquired infection were performed. A total of 191 patients with laboratory-confirmed COVID-19 were included and 57 patients had 97 secondary infectious events. The most frequent agents were Acinetobacter baumannii (28.9%), Pseudomonas aeruginosa (22.7%) and Klebsiella pneumoniae (14.4%); multi-drug resistance was present in 96% of A. baumannii and in 57% of K. pneumoniae. The most prevalent infection was ventilator-associated pneumonia in 57.9% of patients with bacterial infections, or 17.3% of all COVID-19 patients admitted to the ICU, followed by tracheobronchitis (26.3%). Patients with secondary infections had a longer ICU stay (40.0 vs. 17 days; p < 0.001), as well as a longer duration of MV (24.0 vs 9.0 days; p= 0.003). There were 68 (35.6%) deaths overall, of which 27 (39.7%) patients had bacterial infections. Among the 123 survivors, 30 (24.4%) had a secondary infections (OR 2.041; 95% CI 1.080 - 3.859). A high incidence of secondary infections, mainly caused by gram-negative bacteria has been observed. Secondary infections were associated with longer ICU stay, MV use and higher mortality.

Patrones de susceptibilidad de gramnegativos en un hospital pediátrico de tercer nivel: 2013 vs. 2018 / Gram-negative susceptibility patterns in a tertiary pediatric hospital: 2013 vs. 2018

Resumen Introducción: Los gramnegativos continúan siendo los causantes de infecciones asociadas a la atención a la salud (IAAS). Material y métodos:: Analizamos la resistencia antimicrobiana de patógenos durante el 2013 vs. 2018 y lo comparamos con lo publicado en 2006 vs. 2012. Resultados: Identificamos nueve patógenos gramnegativos, de un total de 404 aislamientos, con una prevalencia en 2013 (N = 227 [0.22]) vs. 2018 (N = 177 [0.17]) y una incidencia por egresos (6,607 en el 2013 y 7,778 en el 2018) del 3.4 y 2.2% respectivamente. Destacaron tres patógenos: Klebsiella pneumoniae (129 [31.93%]), Pseudomonas aeruginosa (85 [21.03%]) y Escherichia coli (80 [19.80%]). Estos, llamados patógenos ESKAPE-E, prevalecieron como causantes de IAAS. Identificamos un aumento en los patrones de resistencia para muchos patógenos en 2018. Conclusión: La multirresistencia a patógenos ESKAPE-E es un serio problema de salud pública, por carecer de alternativas terapéuticas para enfrentar este reto. Los mapas de resistencia bacteriana ayudan en la prescripción antibiótica.

Abstract Background: Gram-negatives continue to be the cause of infections associated with health care (HCAI). Material and methods: We analyzed the antimicrobial resistance of pathogens during 2013 vs. 2018 and we compare it with what was published in 2006 vs. 2012. Results: We identified 9 gram-negative pathogens, out of a total of 404 isolates, with a prevalence in 2013 (N = 227 [0.22]) vs. 2018 (N = 177 [0.17]) and an incidence due to discharges (6,607 in 2013 and 7,778 in 2018) of 3.4 and 2.2%, respectively.Three pathogens stood out Klebsiella pneumoniae (129 [31.93%]), Pseudomonas aeruginosa (85 [21.03%]) and Escherichia coli (80 [19.80%]). These, called ESKAPE-E pathogens, prevailed as the cause of HCAI. We identified an increase in resistance patterns for many pathogens in 2018. Conclusion: Multi-resistance to ESKAPE-E pathogens is a serious public health problem, due to the lack of therapeutic alternatives to face this challenge. Bacterial resistance maps help in antibiotic prescription.

Phenotypic and genotypic characterization of plasmid-mediated AmpC beta-lactamases in enteric Gram-negative bacteria from patients with lower respiratory tract infections in a tertiary hospital, southwest Nigeria

Background: AmpC or class C or group 1 beta lactamases are class C cephalosporinases that hydrolyse a wide variety of beta-lactam antibiotics including alpha methoxy beta-lactams (cefoxitin), narrow and broad spectrum cephalosporins. This study was conducted to characterize plasmid-mediated AmpC producing enteric Gram- negative bacteria from patients with lower respiratory tract infections in Obafemi Awolowo University Teaching Hospital Complex (OAUTHC) Ile Ife, Osun State, Nigeria Methodology: A total of 149 patients with clinical features of lower respiratory tract infections (LRTI) were selected by simple random sampling for the study. All Gram-negative isolates recovered from standard microbiological cultures of respiratory specimens of these patients were tested against cefoxitin, third generation cephalosporins (3GCs), and other antibiotics using the disc diffusion AST method, and also screened for production of AmpC beta-lactamases phenotypically by the CLSI method. Plasmid DNA extraction was carried out on twenty-nine cefoxitin-resistant selected isolates using the Kado and Lin method, while genotypic detection of plasmid-mediated AmpC gene was carried out by the polymerase chain reaction (PCR) assay. Results: The results showed that 204 (43.3%) of 471 isolates recovered from the 149 selected patients were resistant to 3GC in the AST assay, among which 121 (59.3%) were resistant to cefoxitin, and 189 of the 471 isolates (40.1%) were AmpC producers. The AmpC producers concurrently showed multiple resistance pattern to other antibiotics tested in this study. Ninety six percent of the 29 selected isolates for plasmid analysis contained plasmids, 45% of which amplified positive on PCR for CMY, 38% for FOX, and 31% for ACC types of AmpC genes. Conclusion: This study showed a high degree of antibiotic resistance among enteric Gram-negative bacteria recovered from patients with LRTIs, as well as high degree of plasmid-encoded AmpC genes responsible for this high antibiotic resistance among the isolates. Proper antibiotic policy and regulation are required to limit the spread of plasmid mediated AmpC ß-lactamase

Estudio de la Inhibición de formación de biopelículas en cepas de Pseudomonas aeruginosa en presencia de própolis / Inhibition study of biofilms production of Pseudomonas aeruginosa strains in the presence of propolis

Uno de los principales fracasos de los tratamientos antibióticos de las infecciones por P. aeruginosa, es debido a la producción de biopelículas. El objetivo de este trabajo fue estudiar la inhibición de formación de biopelículas en cepas de Pseudomonas aeruginosa en presencia de própolis. A todas las cepas se les determinó el perfil de susceptibilidad y se hicieron pruebas de sinergismo. Se detectó el nivel de producción de biopelículas sobre membranas de nitrocelulosa y por microscopía electrónica de transmisión. Se estudió la inhibición de las biopelículas por própolis por dilución en placas. En el hospital de Cumaná, "Dr. Julio Rodríguez", se aislaron cepas de P. aeruginosa, de diferentes procesos infecciosos, principalmente, pie diabético. Todas las cepas produjeron biopelículas a diferentes niveles (leve 60%, moderado 24% e intenso 16%). Sesenta por ciento de las cepas son productoras de MBL y 49% de AmpC. El antibiotipo predominante fue la resistencia a aminoglucósidos y fluoroquinolonas (XII). Siete cepas fueron resistentes a colistin. Las biopelículas tratadas con própolis (10 µg/ml), fueron inhibidas con éxito en su casi totalidad. En conclusión, el própolis logró erradicar la formación de biopelículas in vitro, rompiendo las barreras de los diferentes mecanismos de resistencia a los antibióticos expresados por las cepas de P. aeruginosa estudiadas en este trabajo

One of the main failures of antibiotics treatments of P. aeruginosa infections is due to the production of biofilms. The objective of this work was to study the inhibition of biofilm production in Pseudomonas aeruginosa strains in the presence of propolis. Susceptibility testing and synergism were performed in all strains. Biofilm production level was determined onto nitrocellulose membranes and transmission electronic microscopy. Biofilm inhibition propolis was did on plate dilution. "Dr. Julio Rodríguez" hospital, in Cumaná, P. aeruginosa strains were isolated from different infectious processes, mainly diabetic foot. All the strains produced biofilm at different levels (60% mild, 24% moderate and 16% high). Sixty percent of the strains are producers of MBL, and 49% of AmpC. The predominant antibiotype was resistance to aminoglycosides and fluoroquinolones (XII). Seven strains were resistant's to colistin. Biofilms treated with propolis (10 µg/ml) were almost completely inhibited. In conclusion, the propolis achieved to eradicate the in vitro biofilm production, breaking the barriers of the different mechanisms of resistance to the antibiotics expressed by the P. aeruginosa strains studied in this work

Caracterización y asociación clínico bacteriológica en la espondilodiscitis piógena / Bacteriological-clinical association and characterization in Pyogenic Spondylodiscitis

Resumen: Objetivo: Determinar la asociación entre las características clínicas y estudios de laboratorio con el tipo de microorganismo aislado en hemocultivos de pacientes con espondilodiscitis piógena. Material y métodos: Es un estudio transversal analítico, se revisaron expedientes clínicos de pacientes con espondilodiscitis piógena desde Enero de 2013 hasta Enero de 2017. Se realizó análisis descriptivo univariado usando frecuencias y porcentajes para variables cualitativas, medidas de tendencia central y dispersión para las cuantitativas. Análisis bivariado mediante prueba de χ2 o test exacto de Fisher. Análisis de variables cuantitativas mediante t Student o U de Mann-Whitney. Se usó coeficiente de correlación de Spearman. Considerando significancia estadística p < 0.05. Resultados: Se obtuvo una muestra de 34 pacientes, 20 (58%) fueron mujeres, mediana (Me) de edad 60 años (52-66). Se aisló en hemocultivos, bacterias Gram positivas 11 (32.4%) y Gram negativas 23 (67.6%). El microorganismo aislado más frecuente fue Escherichia coli 12 (35.3%). Los pacientes con espondilodiscitis por Gram negativas presentaron dolor leve y velocidad de sedimentación globular (VSG) Me 26 mm/hra P (18-36), los pacientes con espondilodiscitis por Gram positivas presentaron dolor severo y VSG Me 38 mm/h P (34-40) (p = 0.000 y 0.028, respectivamente). La VSG y dolor en el grupo de pacientes con espondilodiscitis por bacterias Gram negativas tuvo un coeficiente de correlación de Spearman moderado 0.418, (p = 0.047); en el grupo de Gram positivas, un coeficiente de correlación de Spearman bajo 0.228, (p = 0.507). Conclusión: Existe una asociación clínica y estadística de manera significativa entre los tipos de microorganismo aislado en hemocultivo, la intensidad del dolor valorado en escala visual análoga (EVA) y los niveles de VSG.

Abstract: Objective: Determine the association between clinical characteristics and laboratory studies with the type of isolated microorganism in blood cultures of patients with Pyogenic Spondylodiscitis. Material and methods: It is a cross-analytical study, clinical records of patients with Pyogenic Spondylodiscitis were reviewed from January 2013 to January 2017. Univariate descriptive analysis was performed using frequencies and percentages for qualitative variables, central trend measures and dispersion for quantitative ones. Bivariate analysis by testing of χ2 or Fisher's exact test. Analysis of quantitative variables using T Student or Mann-Whitney U. Spearman's correlation coefficient was used. Considering statistical significance p < 0.05. Results: A sample of 34 patients was obtained, 20 (58%) were women, median (Me) of age 60 years (52-66). Was isolated into blood cultures, Gram-positive bacteria 11 (32.4%) gram negatives 23 (67.6%). The microorganism most common isolate was Escherichia coli 12 (35.3%). Patients with Gram-negative spondylodiscitis had mild pain and globular sedimentation rate (VSG) Me 26 mm/hra P (18-36), patients with Gram-positive spondylodyscitis had severe pain and VSG Me 38 mm/h P (34-40) (p= 0.000 and 0.028, respectively). VSG and pain in the group of patients with gram-negative bacteria spondylodiscitis had a moderate Spearman correlation coefficient of 0.418, (p = 0.047); in the Gram positives group, a low correlation coefficient of Spearman 0.228, (p = 0.507). Conclusion: There is a clinical and statistical association significant between types of isolated microorganism in blood culture, pain intensity valued on analog visual scale (EVA) and VSG levels.

Multirresistência microbiana e opções terapêuticas disponíveis / Microbial multi-resistance and available therapeutic options

JUSTIFICATIVA E OBJETIVOS: Devido ao uso irracional de antimicrobianos e a administração empírica, vários problemas de resistência microbiana surgiram como um novo desafio para a terapêutica, causando elevados índices de mortalidade. Dentre os grupos de micro-organismos relacionados a infecções resistentes destacam-se: Staphylococcus aureus resistente à meticilina e Staphylococcus aureus resistente à vancomicina, Enterococcus sp resistentes a diferentes classes de antimicrobianos, Streptococcus pneumoniae resistente à penicilina, Klebsiella pneumoniae carbapenemase, Pseudomonas aeruginosa e Acinetobacter baumanii resistentes aos carbapenêmicos e ainda as enterobactérias produtoras beta-lactamases de espectro ampliado (ESBL). O objetivo deste estudo foi rever na literatura científica a abordagem do surgimento de micro-organismos multirresistentes e as opções terapêuticas disponíveis no Brasil. CONTEÚDO: Novos antimicrobianos são lançados no mercado com o intuito de alcançar tratamento efetivo para infecções causadas por micro-organismos resistentes. Para abordar os mecanismos de resistência mais comuns, das novas opções terapêuticas disponíveis no Brasil e das novas diretrizes de uso desses fármacos. CONCLUSÃO: Enquanto o uso dos medicamentos antimicrobianos continuarem sendo de modo irresponsável e não for cumpridaa legislação para seu uso, os novos fármacos serão eficazes apenas temporariamente, fazendo constante o problema da multirresistência microbiana.

BACKGROUND AND OBJECTIVES: Due to antibiotics irrational use and the empiric administration, many microbial resistance problems become a new therapeutic challenge, causing elevated mortality rates. Among the microorganisms groups related with resistant infections are: methicillin-resistant and vancomycin-resistant Staphylococcus aureus, multi-resistant Enterococcussp, penicillin-resistant Streptococcus pneumoniae, Klebsiella pneumoniae carbapenemase, carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumanii and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL). The aim of this work was carry out a review of scientific literature in order to discuss the emergence of multidrug-resistant microorganism sand the therapeutic options available in Brazil. CONTENTS: New antimicrobials are launched in order to achieve effective treatment for resistant microorganisms infections. To discuss the most common resistance mechanisms, new therapeutic options available in Brazil and new guidelines for the use of these drugs. CONCLUSION: While the use of antimicrobial drugs to keep so irresponsible and the law for its use not met, the new drugs will be effective only temporarily, keeping constant the microbial multi-resistance problem.

Perfil microbiologico de pacientes con patologia infecciosa del segmento anterior / Patient microbiological profile with infectious pathology of the previous segment

En esta investigación fueron evaluados 286 pacientes con patología infecciosa del segmento anterior y mediante estudio microbiológico se identificaron las bacterias asociadas con la infección. En 286 cultivos bacteriológicos realizados se obtuvieron 177 aislamientos, encontrándose un 73.45 por ciento de flora gran positiva siendo las especies más frecuentes S. Epidermidis 48.46 por ciento, S. Aureus (35.38 por ciento), S.Pneumoniae (4.61 por ciento) y Corynebacterium SP. (2.31 por ciento). El 26.55 por ciento correspondía a bacilos gran negativos de los cuales el 74.47 por ciento son enterobacterias y el 25.53 por ciento microorganismos no fermentados. El mayor porcentaje de aislamientos fue realizado en pacientes con conjuntivitis bacteriana, blefaritis bacteriana, conjuntivitis inespecífica y blefaritis inespecífica.

286 patients with infectious pathology in previous segment were studied and through a microbiological study the bacteria associated with the infection were identified. From the 286 bacteriological samples, 177 were isolated, and from these 73.45 percent of Gram positive flora being the most frequent species S. epidermidis (48.46 percent), S. aureus (35.38 percent), S. pneumonia (4.61 percent)and Corynebacterium sp. (2.31 percent). The 26.55 percent corresponded to Gram negative bacilli of which the 74.47 percent are enterobacterias and the 25.53 percent were non fermented microorganisms. The highest percentages of isolations were conducted in patient with bacterial conjunctivitis, bacterial blepharitis, unspecific conjunctivitis and unspecific blepharitis.Key words: ocular infection, Gram positives and Gram negatives bacterial, bacteriological isolations, S. epidermidis, S. aureus, S. pneumonia, Corynebacterium sp.