What is the impact of SARS-CoV-2 pandemic on antimicrobial stewardship programs (ASPs)? The results of a survey among a regional network of infectious disease centres.

Discontinuation of antimicrobial stewardship programs (ASPs) and increased antibiotic use were described during SARS-CoV-2 pandemic. In order to measure COVID-19 impact on ASPs in a setting of high multidrug resistance organisms (MDRO) prevalence, a qualitative survey was designed. In July 2021, eighteen ID Units were asked to answer a questionnaire about their hospital characteristics, ASPs implementation status before the pandemic and impact of SARS-CoV-2 pandemic on ASPs after the 1st and 2nd pandemic waves in Italy. Nine ID centres (50%) reported a reduction of ASPs and in 7 cases (38.9%) these were suspended. After the early pandemic waves, the proportion of centres that restarted their ASPs was higher among the ID centres where antimicrobial stewardship was formally identified as a priority objective (9/11, 82%, vs 2/7, 28%). SARS-CoV-2 pandemic had a severe impact in ASPs in a region highly affected by COVID-19 and antimicrobial resistance but weaknesses related to the pre-existent ASPs might have played a role.

The risk of infection in patients with multiple sclerosis treated with disease-modifying therapies: A Delphi consensus statement.

The risk of infection associated with immunomodulatory or immunosuppressive disease-modifying drugs (DMDs) in patients with multiple sclerosis (MS) has been increasingly addressed in recent scientific literature. A modified Delphi consensus process was conducted to develop clinically relevant, evidence-based recommendations to assist physicians with decision-making in relation to the risks of a wide range of infections associated with different DMDs in patients with MS. The current consensus statements, developed by a panel of experts (neurologists, infectious disease specialists, a gynaecologist and a neuroradiologist), address the risk of iatrogenic infections (opportunistic infections, including herpes and cryptococcal infections, candidiasis and listeria; progressive multifocal leukoencephalopathy; human papillomavirus and urinary tract infections; respiratory tract infections and tuberculosis; hepatitis and gastrointestinal infections) in patients with MS treated with different DMDs, as well as prevention strategies and surveillance strategies for the early identification of infections. In the discussion, more recent data emerged in the literature were taken into consideration. Recommended risk reduction and management strategies for infections include screening at diagnosis and before starting a new DMD, prophylaxis where appropriate, monitoring and early diagnosis.

Vaccinations in patients with multiple sclerosis: A Delphi consensus statement.

BACKGROUND: Patients with multiple sclerosis (MS) are at increased risk of infection. Vaccination can mitigate these risks but only if safe and effective in MS patients, including those taking disease-modifying drugs. METHODS: A modified Delphi consensus process (October 2017-June 2018) was used to develop clinically relevant recommendations for making decisions about vaccinations in patients with MS. A series of statements and recommendations regarding the efficacy, safety and timing of vaccine administration in patients with MS were generated in April 2018 by a panel of experts based on a review of the published literature performed in October 2017. RESULTS: Recommendations include the need for an 'infectious diseases card' of each patient's infectious and immunisation history at diagnosis in order to exclude and eventually treat latent infections. We suggest the implementation of the locally recommended vaccinations, if possible at MS diagnosis, otherwise with vaccination timing tailored to the planned/current MS treatment, and yearly administration of the seasonal influenza vaccine regardless of the treatment received. CONCLUSION: Patients with MS should be vaccinated with careful consideration of risks and benefits. However, there is an urgent need for more research into vaccinations in patients with MS to guide evidence-based decision making.

Latent tuberculosis infection screening in persons newly-diagnosed with HIV infection in Italy: A multicentre study promoted by the Italian Society of Infectious and Tropical Diseases.

BACKGROUND: The Italian Society of Infectious and Tropical Diseases performed a survey on the application of guidelines for the management of persons living with HIV (PLWH), to evaluate current practice and the yield of screening for latent tuberculosis infection (LTBI) in newly-diagnosed PLWH; in addition, the offer of preventive therapy to LTBI individuals and the completion rate were analysed. MATERIALS AND METHODS: Newly-diagnosed PLWH in nine centres were evaluated retrospectively (2016/2017) using binary and multinomial logistic regression to identify factors associated with LTBI diagnostic screening and QuantiFERON (QFT) results. RESULTS: Of 801 patients evaluated, 774 were studied after excluding active TB. LTBI tests were performed in 65.5%. Prescription of an LTBI test was associated with being foreign-born (odds ratio (OR) 3.19, p < 0.001), older (for 10-year increments, OR 1.22, p = 0.034), and having a CD4 count <100 cells/mm3 vs ≥500 cells/mm3 (OR 2.30, p = 0.044). LTBI was diagnosed in 6.5% of 495 patients evaluated by QFT. Positive results were associated with being foreign-born (relative risk ratio (RRR) 30.82, p < 0.001), older (for 10-year increments, RRR 1.78, p = 0.003), and having a high CD4 count (for 100 cells/mm3 increments, RRR 1.26, p < 0.003). Sixteen LTBI individuals started TB preventive therapy and eight completed it. CONCLUSIONS: LTBI screening is inconsistently performed in newly-diagnosed PLWH. Furthermore, TB preventive therapy is not offered to all LTBI individuals and compliance is poor.

Italian recommendations for influenza and pneumococcal vaccination in adult patients with autoimmune rheumatic diseases.

OBJECTIVES: To provide evidence-based recommendations for vaccination against influenza virus and S. pneumoniae in patients with autoimmune rheumatic diseases (ARDs). METHODS: A Consensus Committee including physicians with expertise in rheumatic and infectious diseases was established by two Italian scientific societies, Società Italiana di Reumatologia (SIR) and Società Italiana di Malattie Infettive e Tropicali (SIMIT). The experts were invited to develop evidence-based recommendations concerning vaccinations in ARDs patients, based on their clinical status before and after undergoing immunosuppressive treatments. Key clinical questions were formulated for the systematic literature reviews, based on the clinical pathway. A search was made in Medline (via PubMed) according to the original MeSH strategy from October 2009 and a keyword strategy from January 2016 up to December 2017, updating existing EULAR recommendations. Specific recommendations were separately voted and scored from 0 (no agreement with) to 100 (maximal agreement) and supporting evidence graded. The mean and standard deviation of the scores were calculated to determine the level of agreement among the experts' panel for each recommendation. Total cumulative agreement ≥70 defined consensus for each statement. RESULTS: Nine recommendations, based on 6 key clinical questions addressed by the expert committee, were proposed. The aim of this work is to integrate the 2011 EULAR recommendations on vaccination against influenza and S. pneumoniae in ARDs patients. An implementation plan was proposed to improve the vaccination status of these patients and their safety during immunosuppressive treatments. CONCLUSIONS: Influenza and pneumococcus vaccinations are effective and safe in patients with ARDs. More efforts should be made to translate the accumulated evidence into practice.

International prevalence and risk factors evaluation for drug-resistant Streptococcus pneumoniae pneumonia.

OBJECTIVE: Streptococcus pneumoniae is the most frequent bacterial pathogen isolated in subjects with Community-acquired pneumonia (CAP) worldwide. Limited data are available regarding the current global burden and risk factors associated with drug-resistant Streptococcus pneumoniae (DRSP) in CAP subjects. We assessed the multinational prevalence and risk factors for DRSP-CAP in a multinational point-prevalence study. DESIGN: The prevalence of DRSP-CAP was assessed by identification of DRSP in blood or respiratory samples among adults hospitalized with CAP in 54 countries. Prevalence and risk factors were compared among subjects that had microbiological testing and antibiotic susceptibility data. Multivariate logistic regressions were used to identify risk factors independently associated with DRSP-CAP. RESULTS: 3,193 subjects were included in the study. The global prevalence of DRSP-CAP was 1.3% and continental prevalence rates were 7.0% in Africa, 1.2% in Asia, and 1.0% in South America, Europe, and North America, respectively. Macrolide resistance was most frequently identified in subjects with DRSP-CAP (0.6%) followed by penicillin resistance (0.5%). Subjects in Africa were more likely to have DRSP-CAP (OR: 7.6; 95%CI: 3.34-15.35, p<0.001) when compared to centres representing other continents. CONCLUSIONS: This multinational point-prevalence study found a low global prevalence of DRSP-CAP that may impact guideline development and antimicrobial policies.

Lung ultrasound in the management of pneumocystis pneumonia: A case series.

Despite the decline in HIV mortality and morbidity, Pneumocystis jirovecii pneumonia (PJP) is still frequently seen, particularly in patients with a low CD4+ cell count. We present a case series where we analyzed the possible role of lung ultrasound (LUS) in the management of PJP in a real-life clinical setting. We describe the ultrasound findings from a consecutive series of six HIV patients hospitalized for PJP, all with a favorable outcome, and evaluated with LUS at admission in our ward and then repeated this once during the hospitalization. Multiple B lines indicating interstitial syndrome were detected at admission in all cases, with a bilateral asymmetric pattern mostly localized in middle and upper lobes. In the follow-up LUS, we noted a substantially improved pattern in all patients, observing a reduction of B lines which correlated with clinical amelioration. One patient at admission and three patients during the follow-up showed lung consolidations with hyperechoic spots inside, that might be typical of the disease. In conclusion, LUS could be a practical and noninvasive imaging tool for supporting diagnosis and treatment response of PJP.

Determinants of patient and health care services delays for tuberculosis diagnosis in Italy: a cross-sectional observational study.

BACKGROUND: Prompt diagnosis of active tuberculosis (TB) has paramount importance to reduce TB morbidity and mortality and to prevent the spread of Mycobacterium tuberculosis. Few studies so far have assessed the diagnostic delay of TB and its risk factors in low-incidence countries. METHODS: We present a cross-sectional multicentre observational study enrolling all consecutive patients diagnosed with TB in seven referral centres in Italy. Information on demographic and clinical characteristics, health-seeking trajectories and patients' knowledge and awareness of TB were collected. Diagnostic delay was assessed as patient-related (time between symptoms onset and presentation to care) and healthcare-related (time between presentation to care and TB diagnosis). Factors associated with patient-related and healthcare-related delays in the highest tertile were explored using uni- and multivariate logistic regression analyses. RESULTS: We enrolled 137 patients, between June 2011 and May 2012. The median diagnostic delay was 66 days (Interquartile Range [IQR] 31-146). Patient-related and healthcare-related delay were 14.5 days (IQR 0-54) and 31 days (IQR: 7.25-85), respectively. Using multivariable analysis, patients living in Italy for < 5 years were more likely to have longer patient-related delay (> 3 weeks) than those living in Italy for > 5 years (Odds Ratio [OR] 3.47; 95% Confidence Interval [CI] 1.09-11.01). The most common self-reported reasons to delay presentation to care were the mild nature of symptoms (82%) and a good self-perceived health (76%). About a quarter (26%) of patients had wrong beliefs and little knowledge of TB, although this was not associated with longer diagnostic delay. Regarding healthcare-related delay, multivariate analysis showed that extra-pulmonary TB (OR 4.3; 95% CI 1.4-13.8) and first contact with general practitioner (OR 5.1; 95% CI 1.8-14.5) were both independently associated with higher risk of healthcare-related delay > 10 weeks. CONCLUSIONS: In this study, TB was diagnosed with a remarkable delay, mainly attributable to the healthcare services. Delay was higher in patients with extra-pulmonary disease and in those first assessed by general practitioners. We suggest the need to improve knowledge and raise awareness about TB not only in the general population but also among medical providers. Furthermore, specific programs to improve access to care should be designed for recent immigrants, at significantly high risk of patient-related delay. TRIAL REGISTRATION: The study protocol was registered under the US National Institute of Health ClinicalTrials.gov register, reference number: NCT01390987 . Study start date: June 2011.

Choroidal neovascular membranes secondary to intraocular tuberculosis misdiagnosed as neovascular age-related macular degeneration.

PURPOSE: Intraocular tuberculosis (IOTB) can be complicated by choroidal neovascularization (CNV). However, when the CNV development is not accompanied by clear signs of inflammation, the etiology can be missed, especially in countries nonendemic for tuberculosis. We describe the clinical and imaging features of CNVs presenting as the first sign of IOTB initially misdiagnosed as exudative age-related macular degeneration (AMD). METHODS: A retrospective review of clinical and imaging data of patients initially misdiagnosed with neovascular AMD later diagnosed with inflammatory CNV secondary to IOTB at tertiary referral centers was conducted. Features of fundus photography, fluorescein angiography, indocyanine green angiography, and enhanced depth imaging optical coherence tomography were analyzed. Distinguishing features between neovascular AMD and IOTB-associated CNV were evaluated. RESULTS: Five patients over 55 years of age, erroneously diagnosed with exudative AMD, were included in the study. Multimodal imaging analysis allowed identification of peculiar choroidal alterations such as choroidal granulomas or choroiditis suggestive for posterior uveitis. Systemic workup for granulomatous uveitis including immunologic investigations such as tuberculin skin test or QuantiFERON TB Gold® and radiologic investigations revealed tubercular etiology in all the cases, allowing correct diagnosis and management of the uveitis and related CNV. CONCLUSIONS: Choroidal neovascularization represents a rare and unusual presenting sign of IOTB that can be misleading especially when it occurs in the elderly living in countries with low prevalence of the disease. Multimodal imaging can be helpful and should be employed, especially in atypical cases of CNV, in order to avoid misdiagnosis and/or diagnostic delays.

Bilateral choroiditis as the only sign of persistent Mycobacterium intracellulare infection following haematogenous spread in an immunocompromised patient.

An immunocompromised patient had positive blood cultures for Mycobacterium intracellulare and no identifiable organ seeding was started on treatment. One month later, the patient was clinically well with negative blood cultures but drug-induced myelotoxicity had developed. Ocular fundus examination at this time revealed bilateral choroidal granulomas which changed patient management.

Socioeconomic status and biomedical risk factors in migrants and native tuberculosis patients in Italy.

Action on social determinants is a main component of the World Health Organization End Tuberculosis (TB) Strategy. The aim of the study was to collect information on socioeconomic characteristics and biomedical risk factors in migrant TB patients in Italy and compare it with data collected among Italian TB patients. A cross-sectional study was conducted among TB patients aged ≥18 years over a 12-months enrolment period in 12 major Italian hospitals. Information on education, employment, housing and income was collected, and European Union Statistics on Income and Living Conditions index was used to assess material deprivation. Among migrants, we also analyzed factors associated with severe material deprivation. Migrants were compared with younger (18-64 years) and older (65+ years) Italians patients. Out of 755 patients enrolled (with a median age of 42 years, interquartile range: 31-53), 65% were migrants. Pulmonary, microbiologically confirmed, and new cases were 80%, 73%, and 87% respectively. Prevalence of co-morbidities (i.e. diabetes, chronic kidney disease, neoplastic diseases and use of immunosuppressive drugs) was lower among migrants compared to Italian TB patients, while indicators of socioeconomic status, income and housing conditions were worst in migrants. Forty-six percent of migrants were severely deprived vs. 9% of Italians (p<0.0001, 11.3% and 5.5% among younger and older Italians, respectively). Among migrants, being male, older, irregular, unemployed, with a shorter time spent in Italy, a lower education level, and without a co-morbidity diagnosis were factors associated with severe material deprivation at multi-variable logistic regression. Moreover, socioeconomic indicators for Italian patients did not differ from those reported for the general Italian population, while migrant TB patients seem to have a higher prevalence of severe material deprivation than other migrants residing in Italy. Intervention to address the needs of this population are urgent.

Exogenous reinfection of tuberculosis in a low-burden area.

PURPOSE: Recurrence of tuberculosis (TB) can be the consequence of relapse or exogenous reinfection. The study aimed to assess the factors associated with exogenous TB reinfection. METHODS: Prospective cohort study based on the TB database, maintained at the Division of Infectious Diseases, Luigi Sacco Hospital (Milan, Italy). Time period: 1995-2010. INCLUSION CRITERIA: (1) ≥2 episodes of culture-confirmed TB; (2) cure of the first episode of TB; (3) availability of one Mycobacterium tuberculosis isolate for each episode. Genotyping of the M. tuberculosis strains to differentiate relapse and exogenous reinfection. Logistic regression analysis was used to assess the influence of risk factors on exogenous reinfections. RESULT: Of the 4682 patients with TB, 83 were included. Of these, exogenous reinfection was diagnosed in 19 (23 %). It was independently associated with absence of multidrug resistance at the first episode [0, 10 (0.01-0.95), p = 0.045] and with prolonged interval between the first TB episode and its recurrence [7.38 (1.92-28.32) p = 0.004]. However, TB relapses occurred until 4 years after the first episode. The risk associated with being foreign born, extrapulmonary site of TB, and HIV infection was not statistically significant. In the relapse and re-infection cohort, one-third of the patients showed a worsened drug resistance profile during the recurrent TB episode. CONCLUSIONS: Exogenous TB reinfections have been documented in low endemic areas, such as Italy. A causal association with HIV infection could not be confirmed. Relapses and exogenous reinfections shared an augmented risk of multidrug resistance development, frequently requiring the use of second-line anti-TB regimens.

Optic nerve head tubercular granuloma successfully treated with anti-VEGF intravitreal injections in addition to systemic therapy.

PURPOSE: To describe a case of optic nerve head tubercular granuloma, unresponsive to conventional therapy (antitubercular drugs and systemic steroids), successfully treated with anti-vascular endothelial growth factor (VEGF) intravitreal injections in addition to systemic drugs. METHODS: Case report. RESULTS: A 44-year-old patient was referred to our clinic for progressive vision decrease in his left eye during the preceding 4 months. A large granuloma infiltrating optic nerve head was visible at funduscopic examination along with diffuse intraocular inflammation. Workup for granulomatous uveitis supported the diagnosis of presumed intraocular tuberculosis. However, the large granulomatous lesion did not show a good response to conventional therapy for tubercular uveitis (antitubercular drugs and systemic steroids). Anti-VEGF (bevacizumab) intravitreal injections were performed as an adjunct to the ongoing therapy. After 2 injections, the patient showed an almost complete regression of the lesion (demonstrated by optical coherence tomography) and a restoration of vision. CONCLUSIONS: Anti-VEGF intravitreal injections should be considered in the treatment of large tubercular granulomatous lesions in addition to conventional systemic therapy. Optical coherence tomography could be a suitable tool for studying and following optic nerve head granulomas.

Mycobacterium tuberculosis Beijing family: analysis of the epidemiological and clinical factors associated with an emerging lineage in the urban area of Milan.

The Mycobacterium tuberculosis Beijing genotype raises major concern because of global spreading, hyper-virulence and association with multi-drug resistance (MDR). The aims of the study were to evaluate role of Beijing family in the epidemiological setting of Milan and to identify predictors associated with the spreading of this lineage. Overall 3830TB cases were included. Beijing family accounted for 100 isolates (2.6%). Prevalence grew from 1.7% to 5.4% in the period 1996-2009. Foreign origin increased significantly the risk of having a Beijing strain: the greatest risk was observed among patients coming either from China [AOR=57.7, 95%CI (26.3-126.8)] or from Former Soviet countries [AOR=33.9, 95%CI (12.8-99.6)]. Also MDR was independently associated with Beijing family [AOR=2.7, 95%CI (1.3-5.8)], whereas male gender and younger age only approximated the statistical significance [p 0.051 and p 0.099, respectively]. However, the percentage of cases attributable to MDR strains decreased over time, both in the Beijing group and in the non-Beijing group. 97 isolates were grouped in 37 sub-lineages: MT11, MT33 were predominant. Beijing family is an emerging lineage in Milan. Origin from countries like China and Ukraine and MDR are significantly associated with Beijing. The broad range of the sub-lineages reflects the recent dynamics of the migration flows to our area. This scenario can prelude to a constant increase in the spreading of Beijing strains in the near future.

Influence of Hospitalization upon Diagnosis on the Risk of Tuberculosis Clustering.

SETTING: Culture-positive tuberculosis (TB) diagnosed in the metropolitan area of Milan (Italy) over a 5-year period (1995-1999). OBJECTIVE: To assess the impact of short-course hospitalization upon diagnosis on the overall risk of TB clustering. DESIGN: Restriction fragment length polymorphism profiles with a similarity of 100% defined a cluster. Uni- and multivariable logistic regression models were performed to assess factors associated with clustering. RESULTS: Among 1139 patients, 392 (34.4%) were hospitalized before or soon after diagnosis, 405 (35.6%) received domiciliary treatment since the diagnosis and 392 (30%) had no information about initial clinical management. One hundred fifteen molecular clusters involving 363 patients were identified. Using multivariable analysis, hospitalization was not significantly associated with clustering (OR 1.06, 95%CI 0.75-1.50, p=0.575). Subjects aged >65 years old (OR 0.60; 95CI%:0.37-0.95; p=0.016) and non-Italian born patients (OR 0.56; 95%CI:0.41-0.76; p<0.001) were running a lower risk of clustering. Conversely, HIV co-infected patients (OR 1.88, 95%CI:1.20-2.95, p=0.006) and those with MDR TB (OR 2.50, 95%CI:1.46-4.25, p=0.001) were significantly more likely to be involved in clusters. CONCLUSION: In our cohort, domiciliary treatment was not associated with TB clustering. Expanding domiciliary treatment upon diagnosis appears as an advisable measure to reduce unnecessary costs for the health care system.

[Recurrent tuberculosis: relapse or reinfection?]. / La tubercolosi ricorrente: recidiva o reinfezione esogena?

Recurrent tuberculosis (TB) is an issue that makes worldwide eradication of the disease difficult, especially in countries with a high incidence of TB. Recurrent TB may be due to relapse of the original episode or to an exogenous reinfection caused by a different strain of Mycobacterium tuberculosis. We performed a meta-analysis of selected studies on recurrent TB from 2000 to 2013, adopting molecular genotyping to discriminate between exogenous reinfection and relapses, in order to specifically evaluate the role of HIV infection in the origin of recurrence. Comparison among the studies was limited by the population heterogeneity of the different studies in terms of epidemiology, health status, and diagnostic and therapeutic approach. However, exogenous reinfections are more common in high-burden countries, where HIV infection plays a major role in increasing the risk of a new infection. In contrast, this finding was not confirmed in low-burden countries. Vice versa, globally recognized factors for TB relapse were low compliance to anti-tuberculous treatment, multidrug resistance and persistence of cavitations in the lung parenchyma. The role of other factors like social conditions (immigration, homelessness, working conditions), co-morbidities (silicosis), and characteristics of anti-TB treatment is still controversial.

Unmasking tuberculosis in the era of antiretroviral treatment.

Tuberculosis (TB) can develop soon after antiretroviral treatment initiation, as the result of restoration of the anti-TB specific immune response. This form of the disease is often defined as "unmasked TB", and it represents a major challenge for severely immune-suppressed HIV-infected subjects initiating treatment. Emergence of previously unrecognised TB disease occurs frequently in countries where TB/HIV co-infection is common, and where antiretroviral treatment has become increasingly accessible. The challenges posed by unmasked TB, such as its high incidence, the lack of reliable diagnostic tools and the uncertainties on its optimal management, may hamper our ability to face the TB/HIV epidemic. Therefore, unmasked TB appears a major threat to global health and poses additional barriers to successful HIV/AIDS care and treatment programmes. This review focuses on the epidemiology, immunopathogenesis and clinical manifestations of unmasked TB, and provides evidence-based recommendations for management and care of the disease.

Impact of switching from an open to a closed infusion system on rates of central line-associated bloodstream infection: a meta-analysis of time-sequence cohort studies in 4 countries.

BACKGROUND: We report a meta-analysis of 4 identical time-series cohort studies of the impact of switching from use of open infusion containers (glass bottle, burette, or semirigid plastic bottle) to closed infusion containers (fully collapsible plastic containers) on central line-associated bloodstream infection (CLABSI) rates and all-cause intensive care unit (ICU) mortality in 15 adult ICUs in Argentina, Brazil, Italy, and Mexico. METHODS: All ICUs used open infusion containers for 6-12 months, followed by switching to closed containers. Patient characteristics, adherence to infection control practices, CLABSI rates, and ICU mortality during the 2 periods were compared by χ(2) test for each country, and the results were combined using meta-analysis. RESULTS: Similar numbers of patients participated in 2 periods (2,237 and 2,136). Patients in each period had comparable Average Severity of Illness Scores, risk factors for CLABSI, hand hygiene adherence, central line care, and mean duration of central line placement. CLABSI incidence dropped markedly in all 4 countries after switching from an open to a closed infusion container (pooled results, from 10.1 to 3.3 CLABSIs per 1,000 central line-days; relative risk [RR], 0.33 [95% confidence interval {CI}, 0.24-0.46]; P <.001). All-cause ICU mortality also decreased significantly, from 22.0 to 16.9 deaths per 100 patients (RR, 0.77 [95% CI, 0.68-0.87]; P <.001). CONCLUSIONS: Switching from an open to a closed infusion container resulted in a striking reduction in the overall CLABSI incidence and all-cause ICU mortality. Data suggest that open infusion containers are associated with a greatly increased risk of infusion-related bloodstream infection and increased ICU mortality that have been unrecognized. Furthermore, data suggest CLABSIs are associated with significant attributable mortality.