Mortality in patients with multidrug-resistant Pseudomonas aeruginosa infections: a meta-analysis

Abstract Pseudomonas aeruginosa is the leading cause of nosocomial infections with high mortality rates owing to the limited therapeutic options for multidrug-resistant Pseudomonas aeruginosa (MDRPA) and metallo-beta-lactamase (MBL)-producing strains. Herein, we present a meta-analysis exploring the association between MDRPA and São Paulo MBL-1 (SPM-1)-producing strains vs. mortality. Online databases were screened to identify studies published between 2006 and 2016. A total of 15 studies, comprising 3,201 cases of P. aeruginosa infection, were included. Our results demonstrated a higher mortality rate among patients infected with MDRPA (44.6%, 363/813) than those with non-MDRPA infection (24.8%, 593/2,388) [odds ratio (OR) 2.39, 95% confidence interval (CI) 1.70-3.36, p <0.00001]. The risk of mortality in patients with non-SPM-1 strains was four times higher than that observed in the patients of the SPM-1 group; however, no statistically significant difference was observed (p = 0.43). In conclusion, the results of our study demonstrated that patients infected with MDRPA had a significantly higher mortality rate than that of patients infected with non-MDRPA strains, especially patients with bloodstream infection (BSI), immunosuppression, and inadequate antimicrobial therapy. The absence of studies on the molecular aspects of blaSPM-1 and its association with mortality limited the analysis; therefore, our results should be interpreted with caution. Our findings also highlight the need for more studies on the molecular aspects of resistance and the peculiarities of different nosocomial settings.

Efecto del tratamiento antibiótico inicial adecuado sobre la mortalidad en pacientes en estado crítico con bacteriemia por Pseudomonas aeruginosa / Effect of adequate initial antimicrobi al therapy on mortality in critical patients with Pseudomonas aeruginosa bacteremia

Introducción. La bacteriemia es una de las infecciones hospitalarias de mayor mortalidad, especialmente en las unidades de cuidados intensivos, donde es más frecuente. Pseudomonas aeruginosa es uno de los causantes de bacteriemia más agresivos. Objetivo. Evaluar la asociación entre el tratamiento antibiótico inicial y la mortalidad hospitalaria en estos pacientes. Materiales y métodos. Se trata de un estudio de cohorte retrospectivo multicéntrico realizado entre 2005 y 2008. Se consideró tratamiento adecuado aquel iniciado en las primeras 48 horas del diagnóstico que incluyera, al menos, una dosis de antibiótico intravenoso al que P. aeruginosa fuera sensible y hubiera sido suministrado en la dosis y frecuencia recomendadas. El desenlace principal fue la mortalidad hospitalaria en un lapso de 30 días. Se hizo pareo según grado de exposición usando índices de propensión y, posteriormente, análisis paramétrico de supervivencia. Resultados. Se incluyeron 164 pacientes. La mediana de edad y la clasificación del APACHE II ( Acute Physiology and Chronic Health Evaluation II ) fue de 56 y 13, respectivamente. Se identificó la fuente de la bacteriemia en 68,3 % de los casos, y la más frecuente fue el tracto respiratorio; 44 % de los pacientes recibió tratamiento inadecuado, y la resistencia bacteriana fue la principal variable asociada. La proporción de incidencia de sepsis grave, choque séptico, falla orgánica múltiple y muerte en el lapso de 30 días fue de 67,7, 50, 41,5 y 43,9 %, respectivamente. El tratamiento adecuado se asoció a una prolongación del tiempo hasta el evento (razón de tiempo ajustada, 2,95, IC 95%, 1,63 a 5,33). Conclusión. El tratamiento antibiótico inicial adecuado es un factor protector contra la mortalidad hospitalaria en pacientes con bacteriemia por P. aeruginosa .

Introduction: Among hospital-acquired infections, bacteremia is one of the leading causes of mortality worldwide, especially among intensive care unit patients, where it is more frequent. Pseudomonas aeruginosa is one of the most aggressive agents causing bacteremia. Objective: To evaluate the association between initial antimicrobial therapy and hospital mortality in these patients. Materials and methods: A multicenter and retrospective cohort study was conducted between 2005 and 2008. Antimicrobial therapy was considered adequate if it included at least one intravenous antibiotic to which the P. aeruginosa isolate was susceptible in vitro, was administered at the recommended dose and frequency for bacteremia, and initiated within the first 48 hours from diagnosis. The main outcome was 30-day hospital mortality. Patients were paired according to exposure level using propensity score matching, and then a parametric survival model was fitted. Results: One hundred and sixty four patients were included. Median age and the APACHE II score were 56 and 13, respectively. The source of bacteremia was identified in 68.3 % of cases, the respiratory tract being the most frequent. Forty-four percent of patients received inadequate therapy, with bacterial resistance as the main associated variable. The incidence of severe sepsis, septic shock, multiple organ failure and death within the first 30 days was 67.7, 50, 41.5 and 43.9%, respectively. Adequate therapy was associated with a longer time to the event (adjusted time ratio, 2.95, 95% CI, 1.63 to 5.33). Conclusion: Adequate initial antimicrobial therapy is a protective factor against hospital mortality in patients with P. aeruginosa bacteremia.

Risk factors for pan-resistant Pseudomonas aeruginosa bacteremia and the adequacy of antibiotic therapy

INTRODUCTION: The aim of this study was to determine risk factors for acquiring carbapenemresistant Pseudomonas aeruginosa bacteremia (CR-PA) and factors associated with in-hospital mortality. METHODS: Seventy-seven cases of bacteremia caused by P. aeruginosa were evaluated in a hospital with high incidence of CR-PA. Clinical and laboratorial factors, and previous use of antibiotics were also evaluated. In one analysis, CR-PA and carbapenem-susceptible P. aeruginosa (CS-PA) bacteremia were compared. A second analysis compared patients who died with survivors. RESULTS: Among 77 P. aeruginosa bacteremia, 29 were caused by CR-PA. Admission to the intensive care unit, higher number of total leukocytes, and previous use of carbapenem were statistically associated with CR-PA. In the multivariate analysis, only previous use of carbapenem (including ertapenem) turned out to be a risk factor for CR-PA (p = 0.014). The 30-day mortality of patients with P. aeruginosa bloodstream infection was 44.8% for CS-PA and 54.2% for patients with CR-PA (p = 0.288). Chronic renal failure, admission to the intensive care unit, mechanical ventilation, and central venous catheter were risk factors for mortality. Incorrect treatment increased mortality of patients with bacteremia caused by CS-PA, but not for CR-SA. The odd ratio of mortality associated with incorrect therapy in patients with CS-PA was 3.30 (1.01-10.82; p = 0.043). The mortality of patients with bacteremia caused by CR-PA was unexpectedly similar regardless of antimicrobial treatment adequacy. CONCLUSION: Appropriate treatment for CS-PA bacteremia initiated within the first 24 hours was associated with lower mortality, but this cannot be extrapolated for CR-PA.

Factors associated with epidemic multiresistant Pseudomonas aeruginosa infections in a hospital with AIDS-predominant admissions

INTRODUCTION: Infections caused by multiresistant Pseudomonas aeruginosa (MR-PA) have been associated with persistent infections and high mortality in acquired immunodeficiency syndrome (AIDS) patients. Therefore, understanding the predisposing factors for infection/colonization by this agent is critical for controlling outbreaks caused by MR-PA in settings with AIDS patients. OBJECTIVEAND METHODS: To analyze the presence of factors associated with the acquisition of an epidemic MR-PA strain in a hospital with AIDS-predominant admission. A case-control study was carried out in which cases and controls were gathered from a prospective cohort of all hospitalized patients in an infectious disease hospital during a five-year study period. RESULTS: Multivariate logistic regression analysis demonstrated that enteral nutrition OR = 14.9), parenteral nutrition (OR = 10.7), and use of ciprofloxacin (OR = 8.9) were associated with a significant and independent risk for MR-PA acquisition. CONCLUSIONS: Although cross-colonization was likely responsible for the outbreaks, the use of ciprofloxacin was also an important factor associated with the acquisition of an epidemic MR-PA strain. More studies are necessary to determine whether different types of nutrition could lead to modification of gastrointestinal flora, thereby increasing the risk for infection/colonization by MR-PA in this population.

Outbreaks, persistence, and high mortality rates of multiresistant Pseudomonas aeruginosa infections in a hospital with AIDS-predominant admissions

INTRODUCTION: Authors have reported increased incidence of multiresistant Pseudomonas aeruginosa (MR-PA) infections worldwide over the last decade. Researchers have proposed multifaceted approaches to control MR-PA infections, but none have been reported in the acquired immunodeficiency syndrome (AIDS) setting. OBJECTIVE AND METHODS: Herein we report the impact of a multifaceted intervention for controlling MR-PA over five years in a hospital with AIDS-predominant admissions and describe the clinical characteristics of MR-PA infection in our patient population. The clinical outcomes of infected patients and molecular characteristics of the isolated strains were used as tools for controlling MR-PA infection rates. RESULTS: Significant temporary decrease of new infections was achieved after intervention, although a high level of diagnostic suspicion of nosocomial infection was maintained. We obtained 35 P. aeruginosa isolates with multiresistant profiles from 13 infected and 3 colonized patients and 2 environmental samples. Most of the patients (94 percent) were immunocompromised with AIDS (n = 10) or HTLV-1 infections (n = 5). Of the followed patients, 67 percent had persistent and/or recurrent infections, and 92 percent died. We observed differences in the antibiotic-resistance pattern of MR-PA infection/colonization during two outbreaks, although the genetic profiles of the tested strains were identical. CONCLUSIONS: Therefore, we concluded that early multidisciplinary interventions are essential for reducing the burden caused by this microorganism in patients with AIDS. Prolonged or suppressive antibiotic-based therapy should be considered for MR-PA infections in patients with AIDS because of the persistence characteristic of MR-PA in these patients.

Red-pink colony-producing Pseudomonas sp. is the causative agent of mass mortality in larvae and post-larvae of Litopenaeus vannamei raised in hatcheries in south Iran

This study aimed to identify the causative of the mass mortality observed in zoeal to post-larval shrimp raised in hatcheries in south Iran. For three consecutive months, samples of nauplii and zoea of Litopenaeus vannamei were collected from an affected hatchery located in the province of Bushehr. Upon culture on marine agar, bacterial colonies that produced white, orange, yellow and red pigments were identified. In the hatcheries in which mass mortality was observed, the water columns of the affected tanks exhibited a red-pink color. Therefore, the bacteria that produced red pigment were selected for further phenotypic characterization using polymerase chain reaction [PCR] and virulence bioassays. Our results indicate that this bacterium belonged the genus Pseudomonas and that it was identical to P. mesophilica and/ anguilliseptica. PCR analysis of this bacterium revealed the production of a 150-bp band that was consistent with the Pseudomonas genus. To determine the pathogenicity of the isolated bacteria in nauplii and post-larvae of L vannamei, we performed bioassay experiments by bath immersion at 27-28°C. Our results showed that culture of nauplii and post-larvae of L. vannamei with the bacteria at a concentration of 1.5-2.0[x] 10[5] CFU/mL in marine broth resulted in a 100% mortality rate 24-48 h post-challenge. In contrast, there was no mortality in the nauplii and post-larvae that were cultured in the absence of bacteria. Upon pathological examination, we found that the color of the larvae was abnormal and pink, with acute necrosis of the entire body 48 h post-challenge

Pseudomonas aeruginosa infections: factors relating to mortality with emphasis on resistance pattern and antimicrobial treatment

A retrospective case-control study was conducted to investigate the risk factors for death among intensive care unit patients with Pseudomonas aeruginosa infection. Out of 131 patients investigated, 67 (51.1 percent) died within 30 days of being diagnosed with this infection. The mean duration of hospital stay before this diagnosis was 28.5 ± 26.5 days. No association was found between bacterial resistance and death in this study (multiresistant p= 0.26; panresistant p= 0.42), but the adequacy of the initial treatment was inversely proportional to the degree of resistance. There was a tendency towards greater mortality among patients who received combination therapy (empirical p= 0.09; definitive p= 0.08), despite the greater frequency of appropriate treatment in these patients and the similar degree of severity in the two groups. This finding may be explained by pharmacodynamic parameters that were not studied or by the extensive use of aminoglycosides in the combination therapy, which play a controversial role in combination therapy due to their potential for renal toxicity. The multivariate analysis in our study demonstrated that age [odds ratio (OR) 1.04], septic shock (OR 15.4) and hypoalbuminemia (OR 0.32) were independent risk factors for death.

Epidemiology and prognosis of Pseudomonas aeruginosa bacteremia in a tertiary care center

Objetivo. Describir la epidemiología y el pronóstico de las bacteremias causadas por P.aeruginosa en un centro hospitalario. Diseño. Análisis retrospectivo. Sitio. Centro hospitalario de tercer nivel en la ciudad de México. Pacientes. Todos los casos de bacteremia por P.aeroginosa diagnosticados de 1981 a 1994. Datos. Se analizaron variables demográficas, clínicas y terapéuticas relevantes. Resultados. Se detectaron 153 episodios de bacteremia con una prevalencia promedio de 4.1 episodios por cada 1000 egresos hospitalarios. Veinticinco por ciento de las infecciones tuviero como origen el tracto biliar, y las enfermedades subyacentes más importantes fueron las neoplasia hematológicas. La mortalidad cruda fue de 46 por ciento (70/153) mientras que la mortalidad de bacteremia nosocomial fue de 47 por ciento (58/124). La mortalidad dentro de las primeras 72 horas fue de 24 por ciento (37/153). En un análisis multivariado se detectaron seis factores de riesgo asociados con la muerte: edad = 40 años, estado de choque, ventilación mecánica, uso previo de antibióticos, esplenectomía y selección inadecuad de antibióticos. Conclusión. Fue importante la identificación de los factores de riesgo y la administración oportuna de los tratamientos empírico y específico para mejorar el pronóstico en este grupo de pacientes graves

Infecciones por pseudomonas en una unidad de cuidados intensivos / Pseudomonas infections in an intensive care unit

Introducción. Uno de los factores más importantes que incrementa la mortalidad del paciente crítico es la infección por Pseudomonas. Objetivo. Analizar los efectos de las infecciones por Pseudomonas en los pacientes críticos. Pacientes y métodos. Estudiamo duarante tres años los pacientes que ingresaron a una UCI de Mazatlán, México. Se dividieron en tres grupos: A) Sin infecciones, B) Infecciones por Pseudomonas, y C) Infecciones debidas a otros gérmenes diferentes a Pseudomonas. Se registraron las variables demográficas como edad, sexo, diagnóstico inicial, días de ventilación mecánica (VM), uso de bloqueadores H-2 (BLH), días de estancia y mortalidad. Resultados. Novecientos ochenta y cinco pacientes no infectados (grupo A) tuvieron una mortalidad de 16 por ciento debido a falla orgánica múltiple. Cuarenta y cinco pacientes (grupo B) infectados con Pseudomonas de diferente sitios tuvieron una mortalidad del 63 por ciento; 37 de ellos recibieron BLH y VM. En 101 pacientes (70 por ciento con VM y tratados con BLH grupo C) se aislaron varios gérmenes y la mortalidad fue de 44 por ciento. Se observó una diferencia significativa entre los tres grupos en días de estancia y días de VM (p < 0.001) pero fue variable en relación a la mortaliada, uso de BLH y húesped inmunocomprometido. Conclusión. Las infecciones por Pseudomonas incrementan la mortalidad de los pacientes críticos

Septicemia por pseudomonas en un hospital pediátrico de tercer nivel / Septicemia by pseudomonas in a pedriatric hospital of trird level

Objetivo: Se realizó un estudio retrospectivo para estimar la frecuencia de septicemia por Pseudomonas aeruginosa y pseudomonas sp en el Hospital de Pediatría CMN IMSS, así como evaluar la respuesta clínica a los tratamientos actualmente utilizados. Sujetos y métodos: Se incluyeron todos los pacientes con aislamiento de Pseudomonas en hemocultivo en el periodo comprendido entre octubre de 1990 y abril de 1992. Resultados: Se diagnosticó un total de 15 pacientes. Unicamente 12 recibieron tratamiento. El esquema empírico utilizando en pacientes con fiebre y neutropenia sin foco infeccioso identificado fue carbenicilina-amikacina, que se indicó en 7 pacientes. Seis de doce pacientes que recibieron tratamiento fallecimiento se asoció con un tratamiento antimicrobiano inadecuado y en los otros tres hubo falla terapéutica al tratamiento empírico, sólo una de las cepas aisladas de estos tres pacientes era sensible o medianamente sensible a uno o ambos antimicrobianos utilizados, 5 cepas fueron resistentes a carbenicilina, 4 a amikacina, 8 a gentamicina, 10 a cefotaxima, 3 resistentes a ceftazidima y 2 resistentes a imipenem/cilastatín. Conclusiones: La elevada mortalidad que sigue presentándose en relación con la infección por estos gérmenes no obliga a considerar otras opciones terapéuticas. Se sugiere el uso de ceftazidima-amikacina cuando se tenga certeza bacteriológica y el cambio a imipenem-cilastatín/amikacina si la cepa es resistente o no hay respuesta al tratamiento inicial. No se recomienda la monoterapia