Gram-negative central line-associated bloodstream infection incidence peak during the summer: a national seasonality cohort study.

Central line-associated bloodstream infections (CLABSI) cause increased morbidity, mortality, and hospital costs that are partially preventable. The phenomenon of seasonality among CLABSI rates has not been fully elucidated, but has implications for accurate surveillance and infection prevention trials. Longitudinal dynamic cohort of hospitals participating in hospital-wide and intensive care unit bloodstream infection surveillance for at least one full year over 2000 to 2014. Mixed-effects negative binomial regression analysis calculated the peak-to-low ratio between months as an adjusted CLABSI incidence rate ratio (IRR) with 95% confidence intervals (CI). Multivariate regression models examined the associations between CLABSI pathogens and ambient temperature and relative humidity. The study population included 104 hospital sites comprising 11,239 CLABSI. Regression analysis identified a hospital-wide increase in total CLABSI during July-August, with a higher gram-negative peak-to-low incidence rate ratio (IRR 2.52 [95% CI 1.92-3.30], p < 0.001) compared to gram-positive bacteria (IRR 1.29 [95% CI 1.11-1.48], p < 0.001). Subgroup analysis replicated this trend for CLABSI diagnosed in the intensive care unit. Only gram-negative CLABSI rates were associated with increased temperature (IRR + 30.3% per 5 °C increase [95% CI 17.3-43.6], p < 0.001) and humidity (IRR + 22.9% per 10% increase [95% CI 7.7-38.3), p < 0.001). The incidence and proportion of gram-negative CLABSI approximately doubled during the summer periods. Ambient temperature and humidity were associated with increases of hospital-acquired gram-negative infections. CLABSI surveillance, preventive intervention trials and epidemiological studies should consider seasonal variation and climatological factors when preparing study designs or interpreting their results.

Seasonal variation of hospital-acquired bloodstream infections: A national cohort study.

BACKGROUND: Hospital-acquired bloodstream infections (HABSIs) cause increased morbidity, mortality, and hospital costs that are partially preventable. HABSI seasonality has been described for gram-negative bacteria but has not been stratified per infection origin. OBJECTIVE: To assess seasonality among all types of HABSIs and their associations with climate. METHODS: Hospitals performing surveillance for at least 1 full calendar year between 2000 and 2014 were included. Mixed-effects negative binomial regression analysis calculated the peak-to-low monthly ratio as an adjusted HABSI incidence rate ratio (IRR) with 95% confidence intervals (CIs). Another regression model examined associations between HABSI rates and climate variables. These analyses were stratified by microorganism and infectious origin. RESULTS: The study population included 104 hospitals comprising 44,111 HABSIs. Regression analysis identified an incidence rate ratio (IRR) peak in August for gram-negative HABSIs (IRR, 1.59; 95% CI, 1.49-1.71), CLABSIs (IRR, 1.49; 95% CI, 1.30-1.70), and urinary tract HABSI (IRR, 1.52; 95% CI, 1.34-1.74). The gram-negative incidence increased by 13.1% (95% CI, 9.9%-16.4%) for every 5°C increase in temperature. Seasonality was most present among E. coli, K. pneumoniae, E. cloacae, and the nonfermenters. Gram-positive and pulmonary HABSIs did not demonstrate seasonal variation. CONCLUSIONS: Seasonality with summer spikes occurred among gram-negative bacteria, CLABSIs, and urinary tract HABSIs. Higher ambient temperature was associated with gram-negative HABSI rates. The preventable causative factors for seasonality, such as the nurse-to-patient ratio, indoor room temperature or device-utilization, need to be examined to assess areas for improving patient safety.

Real-life effectiveness of omalizumab in difficult-to-treat versus severe asthma: a national cohort study in Belgium.

BACKGROUND: Guidelines recommend omalizumab in patients with uncontrolled severe allergic asthma. We investigated real-life use of omalizumab, the proportion of patients fulfilling eligibility criteria, its costs and its effectiveness. METHOD: In a cohort of asthma patients initiating treatment with omalizumab in Belgium between 2010 and 2016, we investigated fulfilment of eligibility criteria (chronic use of high-dose inhaled corticosteroids (ICSs) plus long-acting ß2-agonists (LABAs) and ≥2 severe asthma exacerbations in previous year), and compared hospitalisations and systemic corticosteroid consumption in the year before and after omalizumab initiation. We computed healthcare costs in the respective time periods and compared the cost per prevented hospitalisation in patients fulfilling eligibility criteria versus those who did not. RESULTS: Between 2010 and 2016, omalizumab treatment was initiated in 2068 patients with asthma; only 24% fulfilled the eligibility criteria, mainly due to nonadherence to high-dose ICSs + LABAs. The proportion of patients hospitalised for asthma decreased from 41% to 21% in eligible patients (absolute risk reduction, 20%), whereas the absolute risk reduction was 5% (from 19% to 14%) in noneligible patients. The cost per prevented hospitalisation was €44 238 versus €139 495, respectively. Chronic use of systemic corticosteroids was discontinued in 35% of eligible patients versus 15% of noneligible patients. CONCLUSION: In Belgium, omalizumab is mostly initiated in uncontrolled asthma patients who are nonadherent to ICSs + LABAs. Omalizumab decreases hospitalisations and the use of systemic corticosteroids, but at a high cost. Careful management of patients with difficult-to-treat asthma should be a priority before prescribing omalizumab.

Increasing burden of Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecium in hospital-acquired bloodstream infections (2000-2014): A national dynamic cohort study.

The epidemiology of hospital-acquired bloodstream infections (HABSIs) based on the Belgian national surveillance program was analyzed (2000-2014). Our mixed-effects regression analysis identified increased rates of Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecium. HABSI incidence and resistance patterns should be further monitored because of their impact on proper empiric antibiotic therapy.

Poor adherence to guidelines for preventing central line-associated bloodstream infections (CLABSI): results of a worldwide survey.

BACKGROUND: Central line-associated bloodstream infections (CLABSI) are a cause of increased morbidity and mortality, and are largely preventable. We documented attitudes and practices in intensive care units (ICUs) in 2015 in order to assess compliance with CLABSI prevention guidelines. METHODS: Between June and October 2015, an online questionnaire was made available to medical doctors and nurses working in ICUs worldwide. We investigated practices related to central line (CL) insertion, maintenance and measurement of CLABSI-related data following the SHEA guidelines as a standard. We computed weighted estimates for high, middle and low-income countries using country population as a weight. Only countries providing at least 10 complete responses were included in these estimates. RESULTS: Ninety five countries provided 3407 individual responses; no low income, 14 middle income (MIC) and 27 high income (HIC) countries provided 10 or more responses. Of the total respondents, 80% (MIC, SE = 1.5) and 81% (HIC, SE = 1.0) reported availability of written clinical guidelines for CLABSI prevention in their ICU; 23% (MIC,SE = 1.7) and 62% (HIC,SE = 1.4) reported compliance to the following (combined) recommendations for CL insertion: hand hygiene, full barrier precaution, chlorhexidine >0.5%, no topic or systemic antimicrobial prophylaxis; 60% (MIC,SE = 2.0) and 73% (HIC,SE = 1.2) reported daily assessment for the need of a central line. Most considered CLABSI measurement key to quality improvement, however few were able to report their CLABSI rate. Heterogeneity between countries was high and country specific results are made available. CONCLUSIONS: This study has identified areas for improvement in CLABSI prevention practices linked to CL insertion and maintenance. Priorities for intervention differ between countries.

Validation of a Sampling Method to Collect Exposure Data for Central-Line-Associated Bloodstream Infections.

OBJECTIVE: Surveillance of central-line-associated bloodstream infections requires the labor-intensive counting of central-line days (CLDs). This workload could be reduced by sampling. Our objective was to evaluate the accuracy of various sampling strategies in the estimation of CLDs in intensive care units (ICUs) and to establish a set of rules to identify optimal sampling strategies depending on ICU characteristics. DESIGN: Analyses of existing data collected according to the European protocol for patient-based surveillance of ICU-acquired infections in Belgium between 2004 and 2012. SETTING AND PARTICIPANTS: CLD data were reported by 56 ICUs in 39 hospitals during 364 trimesters. METHODS: We compared estimated CLD data obtained from weekly and monthly sampling schemes with the observed exhaustive CLD data over the trimester by assessing the CLD percentage error (ie, observed CLDs - estimated CLDs/observed CLDs). We identified predictors of improved accuracy using linear mixed models. RESULTS: When sampling once per week or 3 times per month, 80% of ICU trimesters had a CLD percentage error within 10%. When sampling twice per week, this was >90% of ICU trimesters. Sampling on Tuesdays provided the best estimations. In the linear mixed model, the observed CLD count was the best predictor for a smaller percentage error. The following sampling strategies provided an estimate within 10% of the actual CLD for 97% of the ICU trimesters with 90% confidence: 3 times per month in an ICU with >650 CLDs per trimester or each Tuesday in an ICU with >480 CLDs per trimester. CONCLUSION: Sampling of CLDs provides an acceptable alternative to daily collection of CLD data.

The Belgian policy of funding antimicrobial stewardship in hospitals and trends of selected quality indicators for antimicrobial use, 1999-2010: a longitudinal study.

OBJECTIVES: In order to improve antimicrobial (AM) use, a policy of providing technical and financial support to AM management teams (AMTs) was rolled out in all Belgian hospitals between 2002 and 2008. We aimed to analyse the association of this policy with AM use for the two indications accounting for the largest number of patients receiving AM: prophylaxis for major lower limb orthopaedic surgery and pneumonia. DESIGN, SETTING, PARTICIPANTS: We used patient-level data routinely collected in all Belgian acute care hospitals between 1999 and 2010. We modelled trends for selected quality indicators (QIs) using the year of AMT implementation in each hospital as the main 'change point', with fine-tuned case-mix adjustment. Of all admissions for lower limb orthopaedic surgery, and pneumonia between 1999 and 2010, 90% (325 094) and 95% (327 635), respectively, were found eligible for analyses. OUTCOMES: The surgery QI was defined as: cefazolin, dose in the expected range, and no use of other AM. For pneumonia, QIs were: ratio of oral/parenteral defined daily doses (DDD, O/P QI), and mean number of DDD minus penicillin, per 100 days of hospitalisation (DDD QI). RESULTS: Between 1999 and 2010, the surgery QI improved from 59% to 71%, the O/P QI from 0.72 to 0.97, and the DDD QI from 96 to 64. Heterogeneity between hospitals was high. Overall, no association was found with the year of implementation of the AMT. CONCLUSIONS: Improvements have been observed but could not be related at the national level to the policy under study. However, these results cannot be extrapolated to other QIs for AM use in hospitals. Our findings do not question the need for AMT, nor the need for continuation of AMT funding. Several recommendations can be made in order to make the best of Belgium's unique political and financial commitments in that field.

Preventable proportion of severe infections acquired in intensive care units: case-mix adjusted estimations from patient-based surveillance data.

BACKGROUND: More than 10% of patients admitted to intensive care units (ICUs) experience a severe, healthcare-associated infection, such as ventilator-associated pneumonia (VAP) or bloodstream infection (BSI). What could be a public health target for prevention is hotly debated, because properly adjusting for intrinsic risk factors in the patient population is difficult. We aimed to estimate the proportion of ICU-acquired VAP and BSI cases that are amenable to prevention in routine conditions. METHODS: We analyzed routine data collected prospectively according to the European standard protocol for patient-based surveillance of healthcare-acquired infections in ICUs. We computed the number of infections to be expected if, after adjustment for case mix, the infection incidence in ICUs with higher infection rates could be reduced to that of the top-tenth-percentile-ranked ICU. Computations came from model-based simulation of individual patient profiles over time in the ICU. The preventable proportion was computed as the number of observed cases minus the number of expected cases divided by the number of observed cases. RESULTS: Data for 78,222 patients admitted for more than 2 days to 525 ICUs in 6 European countries from 2005 to 2008 were available for analysis. We calculated that 52% of VAP and 69% of BSI was preventable. CONCLUSIONS: Our pragmatic, if highly conservative, estimates quantify the potential for prevention of VAP and BSI in routine conditions, assuming that variation in infection incidence between ICUs can be eliminated with improved quality of care, apart from variation attributable to differential case mix.

Impact of availability of guidelines and active surveillance in reducing the incidence of ventilator-associated pneumonia in Europe and worldwide.

BACKGROUND: To analyse whether the availability of written standards for management of mechanically ventilated patients and/or the existence of a surveillance system for cases of ventilation-associated pneumonia (VAP) are positively associated with compliance with 6 well-established VAP prevention measures. METHODS: Ecological study based on responses to an online-questionnaire completed by 1730 critical care physicians. Replies were received from 77 different countries, of which the majority, i.e. 1351, came from 36 European countries. RESULTS: On a cross-country level, compliance with VAP prevention measures is higher in countries with a large number of prevention standards and/or VAP surveillance systems in place at ICU level., Likewise, implementation of standards and VAP surveillance systems has a significant impact on self-reported total compliance with VAP prevention measures (both p < 0.001). Moreover, predictions of overall prevention measure compliance show the effect size of the availability of written standards and existence of surveillance system. For instance, a female physician with 10 years of experience in critical care working in a 15-bed ICU in France has a predicted baseline level of VAP prevention measure compliance of 63 per cent. This baseline level increases by 9.5 percentage points (p < 0.001) if a written clinical VAP prevention standard is available in the ICU, and by another 4 percentage points (p < 0.001) if complemented by a VAP surveillance system. CONCLUSIONS: The existence of written standards for management of mechanically ventilated patients in an ICU and the availability of VAP surveillance systems have shown to be positively associated with compliance with VAP prevention measures and should be fostered on a policy level.

Variations in catheter-related bloodstream infections rates based on local practices.

BACKGROUND: Catheter-related bloodstream infection (CRBSI) surveillance serves as a quality improvement measure that is often used to assess performance. We reviewed the total number of microbiological samples collected in three Belgian intensive care units (ICU) in 2009-2010, and we described variations in CRBSI rates based on two factors: microbiological documentation rate and CRBSI definition which includes clinical criterion for coagulase-negative Staphylococcus (CNS) episode. FINDINGS: CRBSI rates were 2.95, 1.13 and 1.26 per 1,000 estimated catheter-days in ICUs A, B and C, respectively. ICU B cultured fewer microbiological samples and reported the lowest CRBSI rate. ICU C had the highest documentation rate but was assisted by support available from the laboratory for processing single CNS positive blood cultures. With the exclusion of clinical criterion, CRBSI rates would be reduced by 19%, 45% and 0% in ICUs A, B and C, respectively. CONCLUSION: CRBSI rates may be biased by differences of blood culture sampling and CRBSI definition. These observations suggest that comparisons of CRBSI rates in different ICUs remain difficult to interpret without knowledge of local practices.

Prevention of ventilator-associated pneumonia in intensive care units: an international online survey.

BACKGROUND: On average 7% of patients admitted to intensive-care units (ICUs) suffer from a potentially preventable ventilator-associated pneumonia (VAP). Our objective was to survey attitudes and practices of ICUs doctors in the field of VAP prevention. METHODS: A questionnaire was made available online in 6 languages from April, 1st to September 1st, 2012 and disseminated through international and national ICU societies. We investigated reported practices as regards (1) established clinical guidelines for VAP prevention, and (2) measurement of process and outcomes, under the assumption "if you cannot measure it, you cannot improve it"; as well as attitudes towards the implementation of a measurement system. Weighted estimations for Europe were computed based on countries for which at least 10 completed replies were available, using total country population as a weight. Data from other countries were pooled together. Detailed country-specific results are presented in an online additional file. RESULTS: A total of 1730 replies were received from 77 countries; 1281 from 16 countries were used to compute weighted European estimates, as follows: care for intubated patients, combined with a measure of compliance to this guideline at least once a year, was reported by 57% of the respondents (95% CI: 54-60) for hand hygiene, 28% (95% CI: 24-33) for systematic daily interruption of sedation and weaning protocol, and 27% (95%: 23-30) for oral care with chlorhexidine. Only 20% (95% CI: 17-22) were able to provide an estimation of outcome data (VAP rate) in their ICU, still 93% (95% CI: 91-94) agreed that "Monitoring of VAP-related measures stimulates quality improvement". Results for 449 respondents from 61 countries not included in the European estimates are broadly comparable. CONCLUSIONS: This study shows a low compliance with VAP prevention practices, as reported by ICU doctors in Europe and elsewhere, and identifies priorities for improvement.

Impact estimates of nosocomial bloodstream infection: looking from a different angle.

Mortality associated with nosocomial bloodstream infection is multifactorial. Source of infection, etiology, age, underlying disease, acute illness, and appropriateness of antimicrobial therapy all contribute to the final outcome. As such, estimates of mortality attributable to bloodstream infection may differ largely according to the presence or absence of risk factors in distinct patient populations. The adverse effect of nosocomial bloodstream infection for the individual patient is substantial, with about a doubling of the risk of death. Yet, in settings with a high standard of care in terms of infection prevention and control, the occurrence rate of bloodstream infection is relatively low and therefore its impact on overall ICU mortality rather limited. As a consequence, untargeted interventional studies focused on infection prevention should use occurrence rate of infection rather than mortality as outcome variable.

Clinical outcomes of health-care-associated infections and antimicrobial resistance in patients admitted to European intensive-care units: a cohort study.

BACKGROUND: Patients admitted to intensive-care units are at high risk of health-care-associated infections, and many are caused by antimicrobial-resistant pathogens. We aimed to assess excess mortality and length of stay in intensive-care units from bloodstream infections and pneumonia. METHODS: We analysed data collected prospectively from intensive-care units that reported according to the European standard protocol for surveillance of health-care-associated infections. We focused on the most frequent causative microorganisms. Resistance was defined as resistance to ceftazidime (Acinetobacter baumannii or Pseudomonas aeruginosa), third-generation cephalosporins (Escherichia coli), and oxacillin (Staphylococcus aureus). We defined 20 different exposures according to infection site, microorganism, and resistance status. For every exposure, we compared outcomes between patients exposed and unexposed by use of time-dependent regression modelling. We adjusted results for patients' characteristics and time-dependency of the exposure. FINDINGS: We obtained data for 119 699 patients who were admitted for more than 2 days to 537 intensive-care units in ten countries between Jan 1, 2005, and Dec 31, 2008. Excess risk of death (hazard ratio) for pneumonia in the fully adjusted model ranged from 1·7 (95% CI 1·4-1·9) for drug-sensitive S aureus to 3·5 (2·9-4·2) for drug-resistant P aeruginosa. For bloodstream infections, the excess risk ranged from 2·1 (1·6-2·6) for drug-sensitive S aureus to 4·0 (2·7-5·8) for drug-resistant P aeruginosa. Risk of death associated with antimicrobial resistance (ie, additional risk of death to that of the infection) was 1·2 (1·1-1·4) for pneumonia and 1·2 (0·9-1·5) for bloodstream infections for a combination of all four microorganisms, and was highest for S aureus (pneumonia 1·3 [1·0-1·6], bloodstream infections 1·6 [1·1-2·3]). Antimicrobial resistance did not significantly increase length of stay; the hazard ratio for discharge, dead or alive, for sensitive microorganisms compared with resistant microorganisms (all four combined) was 1·05 (0·97-1·13) for pneumonia and 1·02 (0·98-1·17) for bloodstream infections. P aeruginosa had the highest burden of health-care-acquired infections because of its high prevalence and pathogenicity of both its drug-sensitive and drug-resistant strains. INTERPRETATION: Health-care-associated bloodstream infections and pneumonia greatly increase mortality and pneumonia increase length of stay in intensive-care units; the additional effect of the most common antimicrobial resistance patterns is comparatively low. FUNDING: European Commission (DG Sanco).

Development of a clinical scoring system for the diagnosis of smear-negative pulmonary tuberculosis.

This study developed a clinical score based on clinical and radiographic data for the diagnosis of smear-negative pulmonary tuberculosis (SNPT). SNPT was defined as a positive culture in Ogawa in a patient with two negative sputum smears. Data from patients admitted to the emergency ward with respiratory symptoms and negative acid-fast bacilli (AFB) smears was analyzed by means of logistic regression to develop the predictive score.Two hundred and sixty two patients were included. Twenty patients had SNPT. The variables included in the final model were hemoptysis, weight loss, age > 45 years old, productive cough, upper-lobe infiltrate, and miliary infiltrate. With those, a score was constructed. The score values ranged from -2 to 6. The area under the curve for the ROC curve was 0.83 (95% CI 0.74-0.90). A score of value 0 or less was associated with a sensitivity of 93% and a score of more than 4 points was associated with a specificity of 92% for SNPT. Fifty-two point twenty-nine percent of patients had scores of less than one or more than four, what provided strong evidence against and in favor, respectively, for the diagnosis of SNPT. The score developed is a cheap and useful clinical tool for the diagnosis of SNPT and can be used to help therapeutic decisions in patients with suspicion of having SNPT.

Development of a clinical scoring system for the diagnosis of smear-negative pulmonary tuberculosis

This study developed a clinical score based on clinical and radiographic data for the diagnosis of smear-negative pulmonary tuberculosis (SNPT). SNPT was defined as a positive culture in Ogawa in a patient with two negative sputum smears. Data from patients admitted to the emergency ward with respiratory symptoms and negative acid-fast bacilli (AFB) smears was analyzed by means of logistic regression to develop the predictive score.Two hundred and sixty two patients were included. Twenty patients had SNPT. The variables included in the final model were hemoptysis, weight loss, age > 45 years old, productive cough, upper-lobe infiltrate, and miliary infiltrate. With those, a score was constructed. The score values ranged from -2 to 6. The area under the curve for the ROC curve was 0.83 (95 percent CI 0.74-0.90). A score of value 0 or less was associated with a sensitivity of 93 percent and a score of more than 4 points was associated with a specificity of 92 percent for SNPT. Fifty-two point twenty-nine percent of patients had scores of less than one or more than four, what provided strong evidence against and in favor, respectively, for the diagnosis of SNPT. The score developed is a cheap and useful clinical tool for the diagnosis of SNPT and can be used to help therapeutic decisions in patients with suspicion of having SNPT.

Street youths are the only high-risk group for HIV in a low-prevalence South American country.

OBJECTIVES: To measure HIV prevalence in various subpopulations in Bolivia. DESIGN: In 2002 in Cochabamba, we offered voluntary counseling and testing to homeless street youths, registered and unregistered commercial sex workers, truck drivers, and prisoners. We examined surveillance data of pregnant women and blood donors. RESULTS: Among street youths over 15, overall HIV prevalence was 3.5% (11/313), higher among those recruited in the street, lower among those recruited in centers for homeless; prevalence was 0.6% (2/334) and 0.5% (1/189) in female registered and nonregistered sex workers, respectively, and below 0.3% in all other groups. All HIV cases were attributed to sexual transmission. CONCLUSION: In a low-prevalence setting where intravenous drug use is uncommon, street youths are a threat for the expansion of the HIV epidemic. We argue that HIV prevention in this population requires a comprehensive approach to their health and social problems.

Strong general health care systems: a prerequisite to reach global tuberculosis control targets.

We argue that tuberculosis control cannot reach its proposed global targets without investment in an adequate network of accessible, effective and comprehensive health services. Lessons from the past are reviewed. They underscore that passive case-detection and adequate case management is the central technical strategy for tuberculosis control. There is no compelling evidence to support active case-detection in the general population. We elaborate on why a strong health care system is a prerequisite in the framework of case-detection and treatment. The necessity to improve quality and accessibility of general health services for ensuring early detection and subsequent cure is demonstrated. It is argued why the need for strong public health care system becomes even more eminent in the light of the tuberculosis/HIV dual epidemics and of the rapid growth of unregulated private-for-profit services. We finally examine the financial gaps for tuberculosis control and discuss the need for allocating more resources to the strengthening of general health care systems.