Majdi N. Al-Hasan

Overall burden of bloodstream infection and nosocomial bloodstream infection in North America and Europe

In this systematic review, we estimated the total number of episodes of bloodstream infection (BSI) and deaths from BSI per year in North America and Europe, using data from population-based settings. Then, we estimated the number of episodes and deaths from nosocomial BSI from population-based studies and nosocomial infection surveillance systems. We estimated 575 000-677 000 episodes of BSI per year in North America (536 000-628 000 in the USA and 40 000-49 000 in Canada) and 79 000-94 000 deaths (72 000-85 000 in the USA and 7000-9000 in Canada), using estimates from three population-based studies. We estimated over 1 200 000 episodes of BSI and 157 000 deaths per year in Europe, using estimates from one population-based study in each of the following countries: Denmark (9100 episodes and 1900 deaths), Finland (8700 episodes and 1100 deaths) and England (96 000 episodes and 12 000-19 000 deaths). There were substantial differences in estimates of nosocomial BSI between population-based and nosocomial infection surveillance data. BSI has a major impact on the morbidity and mortality of the general population, as it ranks among the top seven causes of death in all included countries in North America and Europe. However, it is difficult to obtain precise estimates of nosocomial BSI, owing to the limited number of studies. This review highlights the need for a greater focus on BSI research in order to reduce the overall burden of disease by improving the outcome of patients with BSI. It also emphasizes the role of infection control and prevention methods in reducing the burden of nosocomial BSI.

Antimicrobial resistance trends of Escherichia coli bloodstream isolates: a population-based study, 1998―2007

BACKGROUND There have been contradictory results regarding temporal changes in the antimicrobial resistance of Escherichia coli from tertiary care centres. Therefore, we performed a population-based investigation to examine in vitro antimicrobial resistance trends of E. coli bloodstream isolates. METHODS In this retrospective population-based incidence study, we identified 461 unique patients with first episodes of E. coli bloodstream infection (BSI) from 1 January 1998 to 31 December 2007 through microbiology records at the two laboratories in Olmsted County, Minnesota. Logistic regression was used to examine temporal changes in antimicrobial resistance and Poisson regression for changes in incidence rates. RESULTS The median age of patients with E. coli BSI was 69 years; 306 (66.4%) were female. The age-adjusted incidence rate of E. coli BSI per 100 000 person-years was 48.0 (95% CI: 42.5-53.4) in females and 34.0 (95% CI: 28.6-39.6) in males. The urinary tract was the most common primary source of infection (79.8%). During the study period, resistance rates of E. coli bloodstream isolates increased from 32% to 53% for ampicillin, from 23% to 45% for ampicillin/sulbactam, from 9% to 28% for trimethoprim/sulfamethoxazole and from 0% to 12% for ciprofloxacin. Resistance rates to carbapenems, cephalosporins and piperacillin/tazobactam remained low and stable. CONCLUSIONS To our knowledge, this is the first population-based study on antimicrobial resistance trends of E. coli bloodstream isolates in the USA. We demonstrated linear trends of increasing resistance among these isolates to three different classes of antimicrobial over the past decade.

Incidence Rate and Outcome of Gram‐Negative Bloodstream Infection in Solid Organ Transplant Recipients

Bacterial infections are common complications of solid organ transplantation (SOT). In this study, we defined the incidence, mortality and in vitro antimicrobial resistance rates of Gram‐negative bloodstream infection (BSI) in SOT recipients. We identified 223 patients who developed Gram‐negative BSI among a cohort of 3367 SOT recipients who were prospectively followed at the Mayo Clinic (Rochester, MN) from January 1, 1996 to December 31, 2007. The highest incidence rate (IR) of Gram‐negative BSI was observed within the first month following SOT (210.3/1000 person‐years [95% confidence interval (CI): 159.3–268.3]), with a sharp decline to 25.7 (95% CI: 20.1–32.1) and 8.2 (95% CI: 6.7–10.0) per 1000 person‐years between 2 and 12 months and more than 12 months following SOT, respectively. Kidney recipients were more likely to develop Gram‐negative BSI after 12 months following transplantation than were liver recipients (10.3 [95% CI: 7.9–13.1] vs. 5.2 [95% CI: 3.1–7.8] per 1000 person‐years). The overall unadjusted 28‐day all‐cause mortality of Gram‐negative BSI was 4.9% and was lower in kidney than in liver recipients (1.6% vs. 13.2%, p < 0.001). We observed a linear trend of increasing resistance among Escherichia coli isolates to fluoroquinolone antibiotics from 0% to 44% (p = 0.002) throughout the study period. This increase in antimicrobial resistance may influence the choice of empiric therapy.

Seasonal variation in Escherichia coli bloodstream infection: a population‐based study

Seasonal variation in the rates of infection with certain Gram-negative organisms has been previously examined in tertiary-care centres. We performed a population-based investigation to evaluate the seasonal variation in Escherichia coli bloodstream infection (BSI). We identified 461 unique patients in Olmsted County, Minnesota, from 1 January 1998 to 31 December 2007, with E. coli BSI. Incidence rates (IR) and IR ratios were calculated using Rochester Epidemiology Project tools. Multivariable Poisson regression was used to examine the association between the IR of E. coli BSI and average temperature. The age- and gender-adjusted IR of E. coli BSI per 100 000 person-years was 50.2 (95% CI 42.9-57.5) during the warmest 4 months (June through September) compared with 37.1 (95% CI 32.7-41.5) during the remainder of the year, resulting in a 35% (95% CI 12-66%) increase in IR during the warmest 4 months. The average temperature was predictive of increasing IR of E. coli BSI (p 0.004); there was a 7% (95% CI 2-12%) increase in the IR for each 10-degree Fahrenheit (c. 5.5 degrees C) increase in average temperature. To our knowledge, this is the first study to demonstrate seasonal variation in E. coli BSI, with a higher IR during the warmest 4 months than during the remainder of the year.

Incidence of Pseudomonas aeruginosa Bacteremia: A Population-Based Study

BACKGROUND The incidence of Pseudomonas aeruginosa bacteremia has not been defined in a population-based investigation. METHODS We performed a retrospective, population-based incidence study using resources of the Rochester Epidemiology Project of Olmsted County, Minnesota. We identified all Olmsted County residents with P. aeruginosa bacteremia between January 1, 1997, and December 31, 2006, by microbiology records in the only 2 laboratories in the county. Medical records were reviewed to confirm diagnosis, residency status, and clinical characteristics. RESULTS Age-adjusted incidence per 100,000 person-years was 10.8 (95% confidence interval [CI], 7.5-14.0) in men and 3.7 (95% CI, 2.2-5.2) in women for total P. aeruginosa bacteremia, and 8.4 (95% CI, 5.5-11.2) in men and 2.5 (95% CI, 1.3-3.8) in women for monomicrobial P. aeruginosa bacteremia. There was no significant change in incidence of total P. aeruginosa bacteremia during the past decade (P=.418). Incidence increased exponentially with age, with a greater magnitude of increase in men compared with women for total and monomicrobial P. aeruginosa bacteremia (P=.007 and P=.015, respectively). In patients with monomicrobial P. aeruginosa bacteremia, the median age was 69 years, and 78.4% of cases were either nosocomial or health care associated. Most patients had multiple comorbid conditions. The urinary tract was the most common primary source of infection. The 28-day all-cause mortality of monomicrobial P. aeruginosa bacteremia was 25.5%. In vitro susceptibility to ciprofloxacin was 95.3%. CONCLUSION To our knowledge, this is the first population-based incidence study of P. aeruginosa bacteremia. The incidence of P. aeruginosa bacteremia has remained stable during the past decade. Fluoroquinolone susceptibility is high among local P. aeruginosa bacteremia isolates.

Bacteremia complicating gram-negative urinary tract infections: A population-based study

BACKGROUND Urinary tract infection (UTI) is common and bacteremia complicating this infection is frequently seen. There has been limited data published that characterize bacteremic UTI in a population-based setting over an extended period. We therefore examined the incidence rate, microbiology, outcome, and in vitro antimicrobial resistance trends of bacteremic UTI due to gram-negative bacilli in Olmsted County, Minnesota, from 1/1/1998 to 12/31/2007. METHODS We used Kaplan-Meier method to estimate mortality rates, Cox proportional hazard regression to determine risk factors for mortality, and logistic regression to examine temporal changes in antimicrobial resistance rates. RESULTS We identified 542 episodes of bacteremic gram-negative UTI among Olmsted County residents during the study period. The median age of patients was 71 years and 65.1% were females. The age-adjusted incidence rate per 100,000 person-years was 55.3 (95% confidence interval [CI]: 49.5-61.2) in females and 44.6 (95% CI: 38.1-51.1) in males. Escherichia coli was the most common pathogen (74.9%). The 28-day and 1-year all-cause mortality rates were 4.9% (95% CI: 3.0-6.8) and 15.6% (95% CI: 12.4-18.8), respectively. Older age was associated with higher mortality; community-acquired infection acquisition and E. coli UTI were both independently associated with lower mortality. During the study period, resistance rates increased linearly from 10% to 24% for trimethoprim-sulfamethoxazole and from 1% to 8% for ciprofloxacin. CONCLUSIONS To our knowledge, this is the first population-based study of bacteremic gram-negative UTI. The linear trend of increasing antimicrobial resistance among gram-negative isolates should be considered when empiric therapy is selected.

Invasive Enteric Infections in Hospitalized Patients With Underlying Strongyloidiasis

Disseminated strongyloidiasis is often associated with enteric bacterial infections. This study was undertaken to determine if enteric organisms caused extraintestinal infections in patients infected with Strongyloides stercoralis but without apparent dissemination. The medical records of hospitalized patients from central Kentucky with strongyloidiasis (1993-2003) were examined to determine the occurrence of extraintestinal infections with enteric organisms. Of 30 patients with S stercoralis, 16 had invasive infections, including sepsis, meningitis, pneumonia, peritonitis, and endocarditis caused by enteric bacteria and Candida organisms. Infections were seen in 8 (62%) of 13 patients with disseminated strongyloidiasis and 8 (47%) of 17 with disease apparently limited to the gastrointestinal tract. Fifteen patients were receiving corticosteroids or other immunosuppressive therapy. Peripheral eosinophilia was seen in only 23% (7/30). Infection with S stercoralis, even without obvious dissemination, may predispose to invasive infections caused by enteric organisms. In Strongyloides-endemic areas, patients with invasive infections caused by enteric organisms should be examined for coinfection with S stercoralis.

Predictive scoring model of mortality in Gram-negative bloodstream infection.

Mortality is a well-recognized complication of Gram-negative bloodstream infection (BSI). The aim of this study was to develop a model to predict mortality in patients with Gram-negative BSI by using the Pitt bacteraemia score (PBS) and other clinical and laboratory variables. A cohort of 683 unique adult patients who were followed for at least 28 days after admission to Mayo Clinic Hospitals with Gram-negative BSI from 1 January 2001 to 31 October 2006 and who received clinically predefined appropriate empirical antimicrobial therapy was retrospectively identified. Multivariable logistic regression was used to identify independent risk factors for 28-day all-cause mortality. Regression coefficients from a multivariable model were used to develop a risk score to predict mortality following Gram-negative BSI. Malignancy (OR 3.48, 95% CI 1.94-6.22), liver cirrhosis (OR 5.42, 95% CI 2.52-11.65), source of BSI other than urinary tract or central venous catheter infection (OR 5.54, 95% CI 2.42-12.69), and PBS (OR 1.98, 95% CI 0.92-4.25 for PBS of 2-3 and OR 6.42, 95% CI 3.11-13.24 for PBS ≥4) were identified as independent risk factors for 28-day mortality in patients with Gram-negative BSI. A risk-score model was created by adding points for each independent risk factor, and had a c-statistic of 0.84. Patients with risk scores of 0, 4, 8, 12 and 16 had estimated 28-day mortality rates of approximately 0%, 3%, 14%, 45%, and 81%, respectively. The Gram-negative BSI risk score described herein estimated mortality risk with high discrimination in patients with Gram-negative BSI who received clinically adequate empirical antimicrobial therapy.

Stratification of the Impact of Inappropriate Empirical Antimicrobial Therapy for Gram-Negative Bloodstream Infections by Predicted Prognosis

ABSTRACT The bloodstream infection mortality risk score (BSIMRS) predicts the outcome of patients with Gram-negative bloodstream infections (BSI) with high discrimination. This retrospective cohort study examined the impact of inappropriate antimicrobial therapy on mortality in adult patients with Gram-negative BSI admitted to Palmetto Health Hospitals in Columbia, SC, USA, from 1 January 2011 to 31 December 2012 after stratification by predicted prognosis at initial presentation using BSIMRS. A multivariate Cox regression model was used to identify independent risk factors for 28-day mortality overall and within each predefined BSIMRS category (<5, 5 to 9, and ≥10). Relative risk reduction (RRR), absolute risk reduction (ARR), and number needed to treat (NNT) were calculated from a predictive logistic regression model of mortality. Overall, 390 unique patients with first episodes of Gram-negative BSI were identified. The median age was 66 years, and 229 (59%) were women. There was significant association between inappropriate antimicrobial therapy and mortality in patients with BSIMRS of 5 to 9 (adjusted hazard ratio [aHR], 3.55; 95% confidence intervals [CI], 1.22 to 8.31; P = 0.02) and BSIMRS of ≥10 (aHR, 4.99; 95% CI, 1.09 to 22.87; P = 0.04) but not in those with BSIMRS of <5 (aHR, 3.34; 95% CI, 0.17 to 22.77; P = 0.34). RRR, ARR, and NNT were 0.25, 0.02, and 63 for BSIMRS of <5; 0.56, 0.32, and 3 for BSIMRS of 5 to 9; and 0.39, 0.39, and 3 for BSIMRS of ≥10, respectively. There is a significant benefit from appropriate antimicrobial therapy in patients with Gram-negative BSI with guarded (BSIMRS of 5 to 9) and poor (BSIMRS of ≥10) predicted prognosis. Survival difference remains unclear among those with good predicted prognosis (BSIMRS of <5) at initial presentation.

Recurrent gram-negative bloodstream infection: a 10-year population-based cohort study.

SUMMARY BACKGROUND Recurrent gram-negative bloodstream infection (BSI) has not been evaluated in a population-based setting; therefore, we performed a population-based retrospective cohort study to examine the incidence, recurrence, and mortality rates of gram-negative BSI. METHODS We identified 944 episodes of gram-negative BSI, including 98 recurrent episodes, among Olmsted County, Minnesota, residents from 1/1/1998 to 12/31/2007. Kaplan-Meier method was used to estimate the cumulative incidence rate of recurrence and 28-day all-cause mortality rate of gram-negative BSI. Cox proportional hazard regression was used to determine risk factors for recurrence. RESULTS The overall age- and gender-adjusted incidence rate of gram-negative BSI per 100,000 person-years was 84.5 (95% confidence interval [CI]: 79.1-90.0), including 75.7 (95% CI: 70.6-80.8) for first episodes and 8.8 (95% CI: 7.1-10.6) for recurrent episodes. Among 846 patients with first episodes of gram-negative BSI, the cumulative incidence rates of recurrence after 1, 5, and 10 years of the initial episode were 5.6%, 9.2%, and 14.6%, respectively, with death treated as a competing risk. Patients with Klebsiella species were more likely than those with Escherichia coli BSI to develop recurrent gram-negative BSI (hazard ratio: 2.33 [95% CI: 1.34-3.92], p=0.003). The 28-day all-cause mortality rates following the initial and second episodes of gram-negative BSI were 10.0% (95% CI: 8.0-12.0) and 11.3% (95% CI: 4.4-18.2), respectively. CONCLUSIONS Even though recurrent gram-negative BSI was relatively uncommon in the general population, up to 15% of patients with gram-negative BSI developed a recurrent episode within 10 years of the initial episode.