International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

Risk of Adverse Reactions to Oral Antibiotics Prescribed by Dentists.

Dentists prescribe a large portion of all oral antibiotics, and these are associated with a risk of adverse drug reactions (ADRs). The aim of this study was to quantify the risk of ADRs associated with oral antibiotics commonly prescribed by dentists. NHS Digital Prescribing data and Yellow Card Drug Analysis data for 2010 to 2017 were abstracted to quantify dental antibiotic prescribing in England, and the rate and types of ADRs associated with them. During the period of study, the mean number of actively practicing dentists in England was 23,624. Amoxicillin accounted for 64.8% of dental antibiotic prescribing and had the lowest reported rate of fatal ADRs (0.1/million prescriptions) and overall ADRs (21.5/million prescriptions). Indeed, amoxicillin was respectively 6 and 3 times less likely to cause an ADR than the other penicillins, penicillin V and amoxicillin + clavulanic acid, and appears to be very safe in patients with no history of penicillin allergy. In contrast, clindamycin, which is often used in patients with penicillin allergy, had the highest rate of fatal (2.9/million prescriptions) and overall (337.3/million prescriptions) ADRs, with Clostridiodes (formerly Clostridium) difficile infections pivotal to its ADR profile. Other amoxicillin alternatives, clarithromycin and metronidazole, while significantly worse than amoxicillin, were 3 and nearly 5 times less likely to cause an ADR than clindamycin. Ranked from least to most likely to cause an ADR, antibiotics most commonly prescribed were as follows: amoxicillin < cephalosporins < erythromycin < tetracyclines < azithromycin < metronidazole < amoxicillin + clavulanic acid < clarithromycin < penicillin V < clindamycin. This study confirmed the high level of safety associated with use of amoxicillin by dentists and the significantly worse rates of fatal and nonfatal ADRs associated with other penicillins and alternatives to amoxicillin for those who are penicillin allergic. In particular, clindamycin had the highest rate of fatal and nonfatal ADRs of any of the antibiotics commonly prescribed by dentists.

International experts' practice in the antibiotic therapy of infective endocarditis is not following the guidelines.

OBJECTIVE: The management of infective endocarditis (IE) may differ from international guidelines, even in reference centres. This is probably because most recommendations are not based on hard evidence, so the consensus obtained for the guidelines does not represent actual practices. For this reason, we aimed to evaluate this question in the particular field of antibiotic therapy. METHODS: Thirteen international centres specialized in the management of IE were selected, according to their reputation, clinical results, original research publications and quotations. They were asked to detail their actual practice in terms of IE antibiotic treatment in various bacteriological and clinical situations. They were also asked to declare their IE-related in-hospital mortality for the year 2015. RESULTS: The global compliance with guidelines concerning antibiotic therapy was 58%, revealing the differences between theoretical 'consensus', local recommendations and actual practice. Some conflicts of interest were also probably expressed. The adherence to guidelines was 100% when the protocol was simple, and decreased with the seriousness of the situation (Staphylococus spp. 54%-62%) or in blood-culture-negative endocarditis (0%-15%) that requires adaptation to clinical and epidemiological data. CONCLUSION: Worldwide experts in IE management, although the majority of them were involved and co-signed the guidelines, do not follow international consensus guidelines on the particular point of the use of antibiotics.

External validation of bloodstream infection mortality risk score in a population-based cohort.

A risk score was recently derived to predict mortality in adult patients with Gram-negative bloodstream infection (BSI). The aim of this study was to provide external validation of the BSI mortality risk score (BSIMRS) in a population-based cohort. All residents of Olmsted County, Minnesota, with Escherichia coli and Pseudomonas aeruginosa BSI from 1 January 1998 to 31 December 2007 were identified. Logistic regression was used to examine the association between BSIMRS and mortality. Area under receiver operating characteristic curve (AUC) was calculated to quantify the discriminative ability of the BSIMRS to predict a variety of short-term and long-term outcomes. Overall, 424 unique Olmsted County residents with first episodes of E. coli and P. aeruginosa BSI were included in the study. Median age was 68 (range 0-99) years, 280 (66%) were women, 61 (14%) had cancer and 9 (2%) had liver cirrhosis. The BSIMRS was associated with 28-day mortality (p <0.001) with an AUC of 0.86. There was an almost 56% increase in 28-day mortality for each point increase in BSIMRS (OR 1.56, 95% CI 1.40-1.78). A BSIMRS ≥ 5 had a sensitivity of 74% and a specificity of 87% to predict 28-day mortality with a negative predictive value of 97%. The BSIMRS had AUC of 0.85, 0.85 and 0.81 for 7-, 14- and 365-day mortality, respectively. BSIMRS stratified mortality with high discrimination in a population-based cohort that included patients of all age groups who had a relatively low prevalence of cancer and liver cirrhosis.

Clinical predictors of recurrent Clostridium difficile infection in out-patients.

BACKGROUND: Clostridium difficile infection (CDI) recurs in 20-30% of patients. AIM: To describe the predictors of recurrence in out-patients with CDI. METHODS: Out-patient cases of CDI in Olmsted County, MN residents diagnosed between 28 June 2007 and 25 June 2010 were identified. Recurrent CDI was defined as recurrence of diarrhoea with a positive C. difficile PCR test from 15 to 56 days after the initial diagnosis with interim resolution of symptoms. Patients who had two positive tests within 14 days were excluded. Cox proportional hazard models were used to assess the association of clinical variables with time to recurrence of CDI. RESULTS: The cohort included 520 out-patients; 104 had recurrent CDI (cumulative incidence of 17.5% by 30 days). Univariate analysis identified increasing age and antibiotic use to be associated with recurrent CDI. Severe CDI, peripheral leucocyte count and change in serum creatinine >1.5-fold were not. In a multiple variable model, concomitant antibiotic use was associated with risk of recurrent CDI (HR = 5.4, 95% CI 1.6-17.5, P = 0.005), while age (HR per 10 year increase = 1.1, 95% CI 0.9-1.3, P = 0.22); peripheral leucocyte count >15 × 10(9) /L (HR = 1.0, 95% CI 0.5-2.1, P = 0.92); and change in serum creatinine greater than 1.5-fold (HR = 0.8, 95% CI 0.4-1.5, P = 0.44) were not. CONCLUSIONS: Antibiotic use was independently associated with a dramatic risk of recurrent Clostridium difficile infection in an out-patient cohort. It is important to avoid unnecessary systemic antibiotics in patients with Clostridium difficile infection, and patients with ongoing antibiotic use should be monitored closely for recurrent infection.

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.

Housing data-based socioeconomic index and risk of invasive pneumococcal disease: an exploratory study.

We previously developed and validated an index of socioeconomic status (SES) termed HOUSES (housing-based index of socioeconomic status) based on real property data. In this study, we assessed whether HOUSES overcomes the absence of SES measures in medical records and is associated with risk of invasive pneumococcal disease (IPD) in children. We conducted a population-based case-control study of children in Olmsted County, MN, diagnosed with IPD (1995-2005). Each case was age- and gender-matched to two controls. HOUSES was derived using a previously reported algorithm from publicly available housing attributes (the higher HOUSES, the higher the SES). HOUSES was available for 92·3% (n = 97) and maternal education level for 43% (n = 45). HOUSES was inversely associated with risk of IPD in unmatched analysis [odds ratio (OR) 0·22, 95% confidence interval (CI) 0·05-0·89, P = 0·034], whereas maternal education was not (OR 0·77, 95% CI 0·50-1·19, P = 0·24). HOUSES may be useful for overcoming a paucity of conventional SES measures in commonly used datasets in epidemiological research.

Outcomes in community-acquired Clostridium difficile infection.

BACKGROUND: Community-acquired Clostridium difficile infection (CA-CDI) is an increasingly appreciated condition. It is being described in populations lacking traditional predisposing factors that have been previously considered at low-risk for this infection. As most studies of CDI are hospital-based, outcomes in these patients are not well known. AIM: To examine outcomes and their predictors in patients with CA-CDI. METHODS: A sub-group analysis of a population-based epidemiological study of CDI in Olmsted county, Minnesota from 1991-2005 was performed. Data regarding outcomes, including severity, treatment response, need for hospitalisation and recurrence were analysed. RESULTS: Of 157 CA-CDI cases, the median age was 50 years and 75.3% were female. Among all CA-CDI cases, 40% required hospitalisation, 20% had severe and 4.4% had severe-complicated infection, 20% had treatment failure and 28% had recurrent CDI. Patients who required hospitalisation were significantly older (64 years vs. 44 years, P < 0.001), more likely to have severe disease (33.3% vs. 11.7%, P = 0.001), and had higher mean Charlson comorbidity index scores (2.06 vs. 0.84, P = 0.001). They had similar treatment failure and recurrence rates as patients who did not require hospitalisation. CONCLUSIONS: Community-acquired Clostridium difficile infection can be associated with complications and poor outcomes, including hospitalisation and severe Clostridium difficile infection. As the incidence of community-acquired Clostridium difficile infection increases, clinicians should be aware of risk factors (increasing age, comorbid conditions and disease severity) that predict the need for hospitalisation and complications in patients with community-acquired Clostridium difficile infection.

Impact of healthcare-associated acquisition on community-onset Gram-negative bloodstream infection: a population-based study: healthcare-associated Gram-negative BSI.

We performed a population-based study to examine the influence of healthcare-associated acquisition on pathogen distribution, antimicrobial resistance, short- and long-term mortality of community-onset Gram-negative bloodstream infections (BSI). We identified 733 unique patients with community-onset Gram-negative BSI (306 healthcare-associated and 427 community-acquired) among Olmsted County, Minnesota, residents from 1 January 1998 to 31 December 2007. Multivariate logistic regression was used to examine the association between healthcare-associated acquisition and microbiological etiology and antimicrobial resistance. Multivariate Cox proportional hazards regression was used to evaluate the influence of the site of acquisition on mortality. Healthcare-associated acquisition was predictive of Pseudomonas aeruginosa (odds ratio [OR] 3.14, 95% confidence intervals [CI]: 1.59-6.57) and the group of Enterobacter, Citrobacter, and Serratia species (OR 2.23, 95% CI: 1.21-4.21) as causative pathogens of community-onset Gram-negative BSI. Healthcare-associated acquisition was also predictive of fluoroquinolone resistance among community-onset Gram-negative bloodstream isolates (OR 2.27, 95% CI: 1.18-4.53). Healthcare-associated acquisition of BSI was independently associated with higher 28-day (hazard ratio [HR] 3.73, 95% CI: 2.13-6.93) and 1-year mortality (HR 3.60, 95% CI: 2.57-5.15). Because of differences in pathogen distribution, antimicrobial resistance, and outcomes between healthcare-associated and community-acquired Gram-negative BSI, identification of patients with healthcare-associated acquisition of BSI is essential to optimize empiric antimicrobial therapy.

Influence of referral bias on the clinical characteristics of patients with Gram-negative bloodstream infection.

Referral bias can influence the results of studies performed at tertiary-care centres. In this study, we evaluated demographic and microbiological factors that influenced referral of patients with Gram-negative bloodstream infection (BSI). We identified 2919 and 846 unique patients with Gram-negative BSI in a referral cohort of patients treated at Mayo Clinic Hospitals and a population-based cohort of Olmsted County, Minnesota, residents between 1 January 1998 and 31 December 2007, respectively. Multivariable logistic regression analysis was used to determine factors associated with referral. Elderly patients aged ≥80 years with Gram-negative BSI were less likely to be referred than younger patients [odds ratio (OR) 0·43, 95% confidence intervals (CI) 0·30-0·62] as were females (OR 0·63, 95% CI 0·53-0·74). After adjusting for age and gender, bloodstream isolates of Escherichia coli (OR 0·50, 95% CI 0·43-0·58) and Proteus mirabilis (OR 0·49, 95% CI 0·30-0·82) were underrepresented in the referral cohort; and Pseudomonas aeruginosa (OR 2·26, 95% CI 1·70-3·06), Enterobacter cloacae (OR 2·31, 95% CI 1·53-3·66), Serratia marcescens (OR 2·34, 95% CI 1·33-4·52) and Stenotrophomonas maltophilia (OR 17·94, 95% CI 3·98-314·43) were overrepresented in the referral cohort. We demonstrated that demographic and microbiological characteristics of patients with Gram-negative BSI had an influence on referral patterns. These factors should be considered when interpreting results of investigations performed at tertiary-care centres.

Epidemiology and outcome of Gram-negative bloodstream infection in children: a population-based study.

Population-based studies of Gram-negative bloodstream infection (BSI) in children are lacking. Therefore, we performed this population-based investigation in Olmsted County, Minnesota, to determine the incidence rate, site of acquisition, and outcome of Gram-negative BSI in children aged ⩽18 years. We used Kaplan-Meier method and Cox proportional hazard regression for mortality analysis. We identified 56 unique children with Gram-negative BSI during the past decade. The gender-adjusted incidence rate of Gram-negative BSI per 100 000 person-years was 129·7 [95% confidence interval (CI) 77·8-181·6]) in infants, with a sharp decline to 14·6 (95% CI 6·0-23·2) and 7·6 (95% CI 4·3-10·9) in children aged 1-4 and 5-18 years, respectively. The urinary tract was the most commonly identified source of infection (34%) and Escherichia coli was the most common pathogen isolated (38%). Over two-thirds (68%) of children had underlying medical conditions that predisposed to Gram-negative BSI. The overall 28-day and 1-year all-cause mortality rates were 11% (95% CI 3-18) and 18% (95% CI 8-28), respectively. Younger age and number of underlying medical conditions were associated with 28-day and 1-year mortality, respectively. Nosocomial or healthcare-associated acquisition was associated with both 28-day and 1-year mortality.

Temporal trends in Enterobacter species bloodstream infection: a population-based study from 1998-2007.

Enterobacter species are the fourth most common cause of Gram-negative bloodstream infection (BSI). We examined temporal changes and seasonal variation in the incidence rate of Enterobacter spp. BSI, estimated 28-day and 1-year mortality, and determined in vitro antimicrobial resistance rates of Enterobacter spp. bloodstream isolates in Olmsted County, Minnesota, from 1 January 1998 to 31 December 2007. Multivariable Poisson regression was used to examine temporal changes and seasonal variation in incidence rate and Kaplan-Meier method was used to estimate 28-day and 1-year mortality. The median age of patients with Enterobacter spp. BSI was 58 years and 53% were female. The overall age- and gender-adjusted incidence rate of Enterobacter spp. BSI was 3.3 per 100,000 person-years (95% CI 2.3-4.4). There was a linear trend of increasing incidence rate from 0.8 (95% CI 0-1.9) to 6.2 (95% CI 3.0-9.3) per 100,000 person-years between 1998 and 2007 (p 0.002). There was no significant difference in the incidence rate of Enterobacter spp. BSI during the warmest 4 months compared to the remainder of the year (incidence rate ratio 1.06; 95% CI 0.47-2.01). The overall 28-day and 1-year mortality rates of Enterobacter spp. BSI were 21% (95% CI 8-34%) and 38% (95% CI 22-53%), respectively. Up to 13% of Enterobacter spp. bloodstream isolates were resistant to third-generation cephalosporins. To our knowledge, this is the first population-based study to describe the epidemiology and outcome of Enterobacter spp. BSI. The increase in incidence rate of Enterobacter spp. BSI over the past decade, coupled with its associated antimicrobial resistance, dictate the need for further investigation of this syndrome.

Risk factor analysis of Histoplasma capsulatum fungemia.

The primary objective of the study was to investigate the risk factors for Histoplasma capsulatum fungemia. We conducted a retrospective case-control study among patients with histoplasmosis seen at Mayo Clinic in Rochester from 1 January 1991 through 31 December 2005. Blood cultures were prepared from specimens obtained from 111 patients with a diagnosis of histoplasmosis of which 55 had demonstrated H. capsulatum fungemia whereas the cultures of the remaining 56 patients were negative. The mean age of the patients was 56 years, of which 70% men and 95% were white. In univariate analysis, immunocompromised status (OR 2.9, P=0.008), peripheral leukocyte count (WBC)<3000 cells/mm(3) (OR 7.3, P<0.001), albumin<3.5 g/ dl (OR 3.1, P=0.018), and Charlson score of>4 (OR 2.9, P=0.022) were associated with H. capsulatum fungemia, but age>55 years was not (OR 1.4, P=0.38). In multivariable analysis, immunocompromised status (OR 2.4, P=0.043) and WBC<3000 cells/mm(3) (OR 6.5, P=0.001) remained significant factors associated with H. capsulatum fungemia. Immunocompromised status and WBC<3000 cells/ mm(3) are independent risk factors for the development of H. capsulatum fungemia.

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.

Evaluation of antibiotic therapy following valve replacement for native valve endocarditis.

We retrospectively evaluated 105 patients at the Mayo Clinic between 1970 and 2006 with native valve endocarditis who underwent acute valve surgery. The objective was to determine if outcomes differed based on whether they had received an antibiotic regimen recommended for native valve endocarditis or one for prosthetic valve endocarditis. Fifty-two patients had streptococcal and 53 had staphylococcal infections. Patients with each type of infection were divided into two groups: the first received postoperative monotherapy (with a beta-lactam or vancomycin), and the second received combination therapy (with an aminoglycoside for streptococcal infection, and gentamicin and/or rifampin for staphylococcal infection). The duration and types of antibiotics given pre- and postoperatively, valve cultures results, antibiotic-related adverse events, relapses, and mortality rates within 6 months of surgery were analyzed. Cure rates were similar regardless of the regimen administered. With the small number of patients in each group, a multicenter study with a larger cohort of patients is needed to better define optimal postoperative treatment regimens in this population.

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.