Baricitinib as rescue therapy in a patient with COVID-19 with no complete response to sarilumab.

A patient with COVID-19-related severe respiratory failure, with insufficient response to an antiretroviral therapy, hydroxychloroquine and Interleukin-6 (IL-6) antagonist therapy, presented a prompt resolution of the respiratory function and improvement in the radiological picture after baricitinib at an oral dose of 4 mg per day for 2 weeks.

Lamivudine-based maintenance antiretroviral therapies in patients living with HIV-1 with suppressed HIV RNA: derivation of a predictive score for virological failure.

OBJECTIVES: Two-drug antiretroviral regimens based on lamivudine (3TC) plus either a protease inhibitor (PI) or dolutegravir (DTG) are becoming increasingly popular in switch strategies. Our goal was to derive a predictive score for virological failure (VF). METHODS: We retrospectively analysed data for a cohort of 587 virologically suppressed (HIV RNA < 37 HIV-1 RNA copies/mL), adult (≥ 18 years old) patients starting lamivudine plus either a boosted PI or dolutegravir. Predictors of VF (defined as a single HIV RNA measurement ≥ 1000 copies/mL or two consecutive HIV RNA measurements ≥ 50 copies/mL) were identified using a multivariate Cox regression model. A 'weighted' score was assigned to each variable associated with VF; the discriminative power of the score obtained was expressed as the area under the receiver-operator characteristic curve (ROC-AUC). RESULTS: During a median 2 years of follow-up time, 35 VFs occurred; predictors of VF were baseline residual HIV RNA between 20 and 36 copies/mL, African ethnicity, ≥ 10 therapeutic lines, the presence of at least one resistance-associated mutation (RAM) for resistance to current drugs (excluding M184V), a non-B viral subtype and a baseline CD4 count < 200 cells/µL. A score of 2 was assigned to non-B viral subtype, 3 to residual viraemia ≥ 20 copies/mL, ≥ 10 previous therapeutic lines and African ethnicity, 4 to baseline CD4 count < 200 cells/µL, and 7 to the presence of at least one RAM (excluding M184V). The ROC-AUC was 0.67 (95% confidence interval 0.57-0.77). CONCLUSIONS: The presence of at least one RAM, higher residual viraemia and African ethnicity were among the major predictors of VF in our cohort. Studies with larger sample sizes are warranted to improve the predictive value of the derived score.

Trends of hospitalisations rates in a cohort of HIV-infected persons followed in an Italian hospital from 1998 to 2016.

Here we evaluated hospitalisation rates and associated risk factors of human immunodeficiency virus (HIV)-infected individuals who were followed up in an Italian reference hospital from 1998 to 2016. Incidence rates (IR) of hospitalisations were calculated for five study periods from 1998 to 2016. The random-effects Poisson regression model was used to assess risk factors for hospitalisation including demographic and clinical characteristics. To consider that more events may occur for the same subject, multiple failure-time data analysis was also performed for selected causes using the Cox proportional hazards model. We evaluated 2031 patients. During 13 173 person-years (py) of follow-up, 3356 hospital admissions were carried out for 756 patients (IR: 255 per 1000 py). IR decreased significantly over the study period, from 634 in 1998-2000 to 126 per 1000 py in 2013-2016. Major declines were detected for AIDS-defining events, non-HIV/AIDS-related infections and neurological diseases. Older age, female sex, longer HIV duration and HCV coinfection were associated with a higher hospitalisation risk, whereas higher CD4 nadir and antiretroviral therapy were associated with a reduced risk. Influence of advanced HIV disease markers declined over time. Hospitalisation rates decreased during the study period in most causes. The relative weight of hospitalisations for non-AIDS-related tumours, cardiovascular, respiratory and kidney diseases increased during the study period, whereas those for AIDS-defining events declined.

A 72-h intervention for improvement of the rate of optimal antibiotic therapy in patients with bloodstream infections.

Antimicrobial stewardship programs are implemented to optimize the use of antibiotics and control the spread of antibiotic resistance. Many antimicrobial stewardship interventions have demonstrated significant efficacy in reducing unnecessary prescriptions of antibiotics, the duration of antimicrobial therapy, and mortality. We evaluated the benefits of a combination of rapid diagnostic tests and an active re-evaluation of antibiotic therapy 72 h after the onset of bloodstream infection (BSI). All patients with BSI from November 2015 to November 2016 in a 1100-bed university hospital in Rome, where an Infectious Disease Consultancy Unit (Unità di Consulenza Infettivologica, UDCI) is available, were re-evaluated at the bedside 72 h after starting antimicrobial therapy and compared to two pre-intervention periods: the UDCI was called by the ward physician for patients with BSI and the UDCI was called directly by the microbiologist immediately after a pathogen was isolated from blood cultures. Recommendations for antibiotic de-escalation or discontinuation significantly increased (54%) from the two pre-intervention periods (32% and 27.2%, p < 0.0001). Appropriate escalation also significantly increased (22.5%) from the pre-intervention periods (8.1% and 8.2%, p < 0.0001). The total duration of antibiotic therapy decreased with intervention (from 21.9 days [standard deviation, SD 15.4] in period 1 to 19.3 days [SD 13.3] in period 2 to 17.7 days in period 3 [SD 11.5]; p = 0.002) and the length of stay was significantly shorter (from 29.7 days [SD 29.3] in period 1 to 26.8 days [SD 24.7] in period 2 to 24.2 days in period 3 [SD 20.7]; p = 0.04) than in the two pre-intervention periods. Mortality was similar among the study periods (31 patients died in period 1 (15.7%), 39 (16.7%) in period 2, and 48 (15.3%) in period 3; p = 0.90). Rapid diagnostic tests and 72 h re-evaluation of empirical therapy for BSI significantly correlated with an improved rate of optimal antibiotic therapy and decreased duration of antibiotic therapy and length of stay.

Multidisciplinary management of pyogenic spondylodiscitis: epidemiological and clinical features, prognostic factors and long-term outcomes in 207 patients.

PURPOSE: Pyogenic spondylodiscitis (PS) is a potentially life-threatening infection burdened by high morbidity rates. Despite the rising incidence, the proper management of PS is still controversial. Aim of this study was to describe the clinical features of PS and to evaluate the prognostic factors and the long-term outcomes of a large population of patients. METHODS: 207 cases of PS treated from 2008 to 2016 with a 2-year follow-up were enrolled. Clinical data from each patient were recorded. The primary outcome was the rate of healing without residual disability. Secondary outcomes included length of stay, healing from infection, death, relapse, and residual disability. Binomial logistic regression and multivariate analysis were used to evaluate prognostic factors. RESULTS: Median diagnostic delay was 30 days and the rate of onset neurological impairment was 23.6%. Microbiological diagnosis was established in 155 patients (74.3%) and the median duration of total antibiotic therapy was 148 days. Orthopedic treatment was conservative for 124 patients and surgical in 47 cases. Complete healing without disability was achieved in 142 patients (77.6%). Statistically confirmed negative prognostic factors were: negative microbiological culture, neurologic impairment at diagnosis and underlying endocarditis (p ≤ 0.05). Healing from infection rate was 90.9%, while residual disabilities occurred in 23.5%. Observed mortality rate was 7.8%. CONCLUSION: The microbiological diagnosis is the main predictive factor for successful treatment. Early diagnosis and multidisciplinary management are also needed to identify underlying aggressive conditions and to avoid neurological complications associated with poorer long-term outcomes. Despite high healing rates, PS may lead to major disabilities still representing a difficult challenge. These slides can be retrieved under Electronic Supplementary material.

New classification for the treatment of pyogenic spondylodiscitis: validation study on a population of 250 patients with a follow-up of 2 years.

PURPOSE: Pyogenic spondylodiscitis (PS) is still burdened by a high rate of orthopedic and neurological complications. Despite the rising incidence, the choice of a proper orthopedic treatment is often delayed by the lack of clinical data. The aim of this study was to propose a clinical-radiological classification of pyogenic spondylodiscitis to define a standard treatment algorithm. METHODS: Based on data from 250 patients treated from 2008 to 2015, a clinical-radiological classification of pyogenic spondylodiscitis was developed. According to primary classification criteria (bone destruction or segmental instability, epidural abscesses and neurological impairment), three main classes were identified. Subclasses were defined according to secondary criteria. PS without segmental instability or neurological impairment was treated conservatively. When significant bone loss or neurological impairment occurred, surgical stabilization and/or decompression were performed. All patients underwent clinical and radiological 2-year follow-up. RESULTS: Type A PS occurred in 84 patients, while 46 cases were classified as type B and 120 as type C. Average time of hospitalization was 51.94 days and overall healing rate was 92.80%. 140 patients (56.00%) were treated conservatively with average time of immobilization of 218.17 ± 9.89 days. Both VAS and SF-12 scores improved across time points in all classes. Residual chronic back pain occurred in 27 patients (10.80%). Overall observed mortality was 4.80%. CONCLUSIONS: Standardized treatment of PS is highly recommended to ensure patients a good quality of life. The proposed scheme includes all available orthopedic treatments and helps spine surgeons to significantly reduce complications and costs and to avoid overtreatment.

Initial antifungal strategy does not correlate with mortality in patients with candidemia.

The incidence of Candida bloodstream infections (BSIs) has increased over time, especially in medical wards. The objective of this study was to evaluate the impact of different antifungal treatment strategies on 30-day mortality in patients with Candida BSI not admitted to intensive care units (ICUs) at disease onset. This prospective, monocentric, cohort study was conducted at an 1100-bed university hospital in Rome, Italy, where an infectious disease consultation team was implemented. All cases of Candida BSIs observed in adult patients from November 2012 to April 2014 were included. Patients were grouped according to the initial antifungal strategy: fluconazole, echinocandin, or liposomal amphotericin B. Cox regression analysis was used to identify risk factors significantly associated with 15-day and 30-day mortality. During the study period, 130 patients with candidemia were observed (58 % with C. albicans, 7 % with C. glabrata, and 23 % with C. parapsilosis). The first antifungal drug was fluconazole for 40 % of patients, echinocandin for 57.0 %, and liposomal amphotericin B for 4 %. During follow-up, 33 % of patients died. The cumulative mortality 30 days after the candidemia episode was 30.8 % and was similar among groups. In the Cox regression analysis, clinical presentation was the only independent factor associated with 15-day mortality, and Acute Physiology and Chronic Health Evaluation (APACHE) II score and clinical presentation were the independent factors associated with 30-day mortality. No differences in 15-day and 30-day mortality were observed between patients with and without C. albicans candidemia. In patients with candidemia admitted to medical or surgical wards, clinical severity but not the initial antifungal strategy were significantly correlated with mortality.

Efficacy and safety of treatment simplification to atazanavir/ritonavir + lamivudine in HIV-infected patients with virological suppression: 144 week follow-up of the AtLaS pilot study.

OBJECTIVES: AtLaS was a single-arm pilot study that demonstrated promising efficacy and safety of treatment simplification to a dual regimen with atazanavir/ritonavir + lamivudine in virologically suppressed HIV-positive patients. Here, we report data from the 144 week follow-up. METHODS: At baseline, patients treated with a three-drug atazanavir/ritonavir-based regimen were switched to 300/100 mg of atazanavir/ritonavir plus 300 mg of lamivudine once daily. Major clinical events, laboratory parameters, neurocognitive performance, bone composition and body fat distribution were monitored. Treatment failure was defined as a discontinuation/switch of the regimen or virological failure (HIV-RNA >50 copies/mL in two consecutive determinations or a single level above 1000 copies/mL). RESULTS: After 144 weeks, 9/40 (22.5%) treatment failures occurred, including two virological failures (Weeks 48 and 53, without resistance). A significant increase in the CD4 count was observed at Week 96 (+124 cells/mm(3); P = 0.002) and Week 144 (+94 cells/mm(3); P = 0.008). After 144 weeks, a significant increase in total cholesterol (+25 mg/dL; P = 0.001), HDL cholesterol (+6 mg/dL; P = 0.024) and LDL cholesterol (+12 mg/dL; P = 0.008) was observed, without any change in triglyceride levels, total cholesterol/HDL ratio or LDL/HDL ratio. A significant increase in the estimated glomerular filtration rate (+25 mL/min/1.73 m(2); P < 0.001) and lumbar spine T-score and Z-score (+0.2, P = 0.011; and +0.35, P = 0.001, respectively) and a decrease in trunk fat (-1.898 g; P = 0.005) were also observed. Neurocognitive function did not decline over time. Concerning safety, 10 moderate to severe adverse events were recorded in eight patients; overall seven cases of renal colic (possibly treatment related) were observed, leading to a discontinuation of treatment in two patients. CONCLUSIONS: Data from the 144 week follow-up suggested good long-term efficacy of the simplification strategy that was investigated, with rare virological failure and a potential for improvement of the CD4 count, renal function and bone mineral density. This strategy warrants further investigation in a randomized trial.

Pharmacokinetics of etravirine in HIV-infected patients concomitantly treated with rifampin for tuberculosis.

Etravirine is metabolized by three cytochrome P450 enzymes that are in turn induced by rifampin. Consequently, co-administration of etravirine and rifampin is not recommended. To date, however, no clinical studies exploring the drug-drug interaction of this combination have been conducted. Here we report two cases of off-label etravirine use concurrently with antitubercular treatment, dictated by the unavailability of other treatments. Plasma drug concentrations were monitored by regular measurements. Our results appear to confirm the increased metabolism of etravirine through the induction of cytochrome P450 enzymes, but the adequacy of drug levels in all of the measurements and subsequent virological suppression suggest that this drug interaction may not be clinically relevant.

Genotypic testing on HIV-1 DNA as a tool to assess HIV-1 co-receptor usage in clinical practice: results from the DIVA study group.

PURPOSE: We have developed a sequencing assay for determining the usage of the genotypic HIV-1 co-receptor using peripheral blood mononuclear cell (PBMC) DNA in virologically suppressed HIV-1 infected patients. Our specific aims were to (1) evaluate the efficiency of V3 sequences in B versus non-B subtypes, (2) compare the efficiency of V3 sequences and tropism prediction using whole blood and PBMCs for DNA extraction, (3) compare the efficiency of V3 sequences and tropism prediction using a single versus a triplicate round of amplification. RESULTS: The overall rate of successful V3 sequences ranged from 100 % in samples with >3,000 copies HIV-1 DNA/10(6) PBMCs to 60 % in samples with <100 copies total HIV-1 DNA /10(6) PBMCs. Analysis of 143 paired PBMCs and whole-blood samples showed successful V3 sequences rates of 77.6 % for PBMCs and 83.9 % for whole blood. These rates are in agreement with the tropism prediction obtained using the geno2pheno co-receptor algorithm, namely, 92.1 % with a false-positive rate (FPR) of 10 or 20 % and of 96.5 % with an FPR of 5.75 %. The agreement between tropism prediction values using single versus triplicate amplification was 98.2 % (56/57) of patients using an FPR of 20 % and 92.9 % (53/57) using an FPR of 10 or 5.75 %. For 63.0 % (36/57) of patients, the FPR obtained via the single amplification procedure was superimposable to all three FPRs obtained by triplicate amplification. CONCLUSIONS: Our results show the feasibility and consistency of genotypic testing on HIV-1 DNA tropism, supporting its possible use for selecting patients with suppressed plasma HIV-1 RNA as candidates for CCR5-antagonist treatment. The high agreement between tropism prediction by single and triple amplification does not support the use of triplicate amplification in clinical practice.

Cardiovascular risk factors and carotid intima-media thickness are associated with lower cognitive performance in HIV-infected patients.

OBJECTIVES: The aim of the study was to investigate the relationship between metabolic comorbidities, cardiovascular risk factors or common carotid intima-media thickness (cIMT) and cognitive performance in HIV-infected patients. METHODS: Asymptomatic HIV-infected subjects were consecutively enrolled during routine out-patient visits at two clinical centres. All patients underwent an extensive neuropsychological battery and assessment of metabolic comorbidities and cardiovascular risk factors. Moreover, cIMT was assessed by ultrasonography. Cognitive performance was evaluated by calculating a global cognitive impairment (GCI) score obtained by summing scores assigned to each test (0 if normal and 1 if pathological). RESULTS: A total of 245 patients (median age 46 years; 84.1% with HIV RNA < 50 copies/mL; median CD4 count 527 cells/µL) were enrolled in the study. Cardiovascular risk factors were highly prevalent in our population: the most frequent were dyslipidaemia (61.2%), cigarette smoking (54.3%) and hypertension (15.1%). cIMT was abnormal (≥ 0.9mm) in 31.8% of patients. Overall, the median GCI score was 2 [interquartile range (IQR) 1-4]; it was higher in patients with diabetes (P = 0.004), hypertension (P = 0.030) or cIMT ≥ 0.9 mm (P < 0.001). In multivariate analysis, it was confirmed that diabetes (P = 0.007) and cIMT ≥ 0.9 mm (P = 0.044) had an independent association with lower cognitive performance. In an analysis of patients on combination antiretroviral therapy (cART), abacavir use was independently associated with a better cognitive performance (P = 0.011), while no association was observed for other drugs or neuroeffectiveness score. CONCLUSIONS: Diabetes, cardiovascular risk factors and cIMT showed a strong association with lower cognitive performance, suggesting that metabolic comorbidities could play a relevant role in the pathogenesis of HIV-associated neurocognitive disorders in the recent cART era.

Comparison of cognitive performance in HIV or HCV mono-infected and HIV-HCV co-infected patients.

PURPOSE: Our aim was to explore the interplay between human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections in the expression of cognitive disorders. METHODS: We performed a multi-centre cross-sectional study, enrolling three groups of asymptomatic outpatients matched for age and education: (1) HIV mono-infected; (2) HCV mono-infected; (3) HIV-HCV co-infected. All subjects were subjected to the Zung depression scale and a comprehensive neuropsychological battery. RESULTS: A total of 50 patients for each group were enrolled. Patients in the three groups did not significantly differ in the main common demographic and clinical characteristics, except for a lower proportion of past injecting drug use (IDU) in group 1 (4 %) in comparison to groups 2 (38 %, p < 0.001) and 3 (78 %, p < 0.001), a longer duration of HIV infection in group 3 in comparison to group 1 (p < 0.001) and a longer duration of HCV infection in group 3 in comparison to group 2 (p = 0.028). Overall, 39.3 % of patients showed minor cognitive impairment, with a higher proportion in group 3 (54 %) when compared to groups 1 (28 %, p = 0.015) or 2 (36 %, p = 0.108). Patients in group 3 [odds ratio (OR) 3.35, p = 0.038 when compared to group 1] and those with higher depression scores (OR 1.05, p = 0.017) showed an increased risk of cognitive impairment after adjusting for education and past injection drug use. In particular, group 3 showed worse performance in psychomotor speed tasks when compared to group 1 (p = 0.033). CONCLUSIONS: A worse cognitive performance in HIV-HCV co-infected patients was observed, suggesting an additive role of the two viruses in the pathogenesis of cognitive disorders.

Health-related quality of life (HRQoL) from HIV patients' perspective: comparison of patient-reported outcome (PRO) measures among people living with hiv (PLWH) and other chronic clinical conditions.

BACKGROUND: People living with HIV (PLWH) are generally known to suffer from a lower quality of life compared to the one of general population, but still very few is known about the self-perception of quality of life when comparing HIV to non-communicable diseases. We performed a comprehensive assessment of patient's reported outcomes measures (PROMs) among PLWH and patients affected by other chronic conditions (OC) such as diabetes mellitus type 1, rheumatoid arthritis, breast cancer in hormonal therapy, in order to investigate differences in PROMs outcomes between PLWH and other pathologies. METHODS: A cross-sectional observational study was performed by using questionnaires investigating health-related quality of life (Medical Outcomes Study Short Form 36-item Health Survey), work productivity (WPI), and global health status (EQ-5D-3L). They were administered to patients affected by chronic diseases consecutively observed at a single University Hospital during a 10 months period, with comparable disease related aspects. Logistic regression analysis was used to analyze the association between disease group (HIV vs OC) and PROMs. RESULTS: 230 patients were enrolled (89 PLWH, 143 OC). Mean age: 49 years (SD 10), mean time of disease 12 years (10), 96% were Caucasian, 35% assumed polypharmacy, 42% of male were PLWH versus 16% OC (p < 0.001), 19% PLWH versus 6% OC had clinical complications (p < 0.001). HIV infection was independently associated to a better health-related quality of life in several domains compared with the other conditions, except in mental health, whereas a worst health-related quality of life in most domains was reported by older patients and those experiencing polypharmacy. CONCLUSIONS: In this cohort of patients with chronic conditions followed within the same health setting, PLWH showed better self-reported health outcomes compared to other chronic conditions with comparable characteristics of chronicity. The potential detrimental role of older age and polypharmacy in most outcomes suggests the need of longitudinal assessment of PROMs in clinical practice.

Exposure to HIV-protease inhibitors selects for increased expression of P-glycoprotein (ABCB1) in Kaposi's sarcoma cells.

BACKGROUND: Given that HIV-protease inhibitors (HIV-PIs) are substrates/inhibitors of the multidrug transporter ABCB1, can induce ABCB1 expression, and are used in combination with doxorubicin for AIDS-Kaposi's Sarcoma (KS) treatment, the role that ABCB1 plays in mediating multidrug resistance (MDR) in a fully transformed KS cell line (SLK) was explored. METHODS: The KS cells were exposed to both acute and chronic treatments of physiological concentrations of different HIV-PIs (indinavir, nelfinavir, atazanavir, ritonavir, or lopinavir), alone or together with doxorubicin. The ABCB1 mRNA and protein expression levels were then assessed by qRT-PCR and western blotting, flow cytometry, and immunofluorescence. RESULTS: Chronic treatment of SLK cells with one of the five HIV-PIs alone or together resulted in increased resistance to doxorubicin. Co-treatment with one of the HIV-PIs in combination with doxorubicin resulted in a synergistic increase in resistance to doxorubicin, and the degree of resistance was found to correlate with the expression of ABCB1. The SLK cells were also revealed to be cross-resistant to the structurally unrelated drug paclitaxel. CONCLUSION: These studies suggest that ABCB1 is primarily responsible for mediating MDR in SLK cells selected with either HIV-PIs alone or in combination with doxorubicin. Therefore, the roles that ABCB1 and drug cocktails play in mediating MDR in KS in vivo should be evaluated.

Clinical presentation, microbiological features and correlates of disease severity of 2009 pandemic influenza A (H1N1) infection.

The purpose of this study was to describe epidemiological, clinical and microbiological characteristics of confirmed novel influenza A (H1N1) infection, investigating factors associated with disease severity. We retrospectively selected patients seeking care for respiratory symptoms in two periods (May-August and September-November 2009) with different epidemiological characteristics. Only patients with confirmed pandemic influenza A (H1N1) were enrolled in this study. A total of 104 patients with H1N1 infection were evaluated, mostly referring classic influenza symptoms; in addition, diarrhea and vomiting were often referred. Clinical signs, symptoms and respiratory complications were different in the two periods. Of all patients, 18 (17%) had pneumonia. Patients older than 50 years showed a lower probability of pneumonia diagnosis when compared to children aged 0-13 (p = 0.049); a longer duration of symptoms before medical care was associated with a higher probability of pneumonia (p = 0.026). Phylogenetic analysis showed a low variability both in hemagglutinin and neuraminidase genes. In addition, no neuraminidase mutation associated with antiviral resistance was detected. A detailed description of respiratory diseases associated with H1N1 infection was provided and factors associated with its severity were investigated, thus contributing to the insight into epidemiological, clinical and microbiological knowledge of the disease.

Relationship between antiretroviral plasma concentration and emergence of HIV-1 resistance mutations at treatment failure.

PURPOSE: The relationship between antiretroviral pharmacokinetic exposure and acquisition of human immunodeficency virus-1 (HIV-1) drug resistance mutations (DRM) is not fully understood. The aim of this study was to investigate whether antiretroviral plasma concentration could predict the emergence of DRM at treatment failure. METHODS: The study cohort comprised retrospectively selected patients with failing antiretroviral regimens for whom a protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) trough concentration measurement (TDM) had been obtained before failure, a genotypic resistance test (GRT1) had been performed before the TDM, and a genotypic resistance test (GRT2) had been performed at therapeutic failure. Drug levels were classified as undetectable/detectable or subtherapeutic/therapeutic according to limits of quantification of a high-performance liquid chromatography-ultraviolet assay or pre-defined efficacy thresholds, respectively. The number of DRM acquired at treatment failure was evaluated by comparing the results of the GRT2 and GRT1. RESULTS: A total of ten and 57 failure episodes occurred among our patients on NNRTI-based and PI-based regimens, respectively, and included in the evaluation. PI concentration was subtherapeutic in 28.1% of patients, among which the levels were undetectable in 21.1%. Twenty-five (43.9%) patients acquired at least one new PI-DRM according to the GRT2. Patients with undetectable PI levels showed a lower emergence of PI-DRM (minor + major) than those with detectable levels (8.3 vs. 53.3%, p = 0.007). Multivariate analysis confirmed that undetectable PI levels were independent negative predictors of DRM selection. NNRTI measurements were subtherapeutic in 2/10 (20%) patients. NNRTI-DRM were acquired by all patients regardless of NNRTI levels. CONCLUSIONS: A PI measurement showing undetectable drug levels prior to treatment failure predicted the lack of emergence of PI-DRM at failure. These results suggest that PI levels can help clinicians interpret the reasons for treatment failure and guide the type of interventions needed.

Multidrug-resistant Pseudomonas aeruginosa bloodstream infections: risk factors and mortality.

We retrospectively studied patients diagnosed with P. aeruginosa bloodstream infections (BSIs) in two Italian university hospitals. Risk factors for the isolation of multidrug-resistant (MDR) or non-MDR P. aeruginosa in blood cultures were identified by a case-case-control study, and a cohort study evaluated the clinical outcomes of such infections. We identified 106 patients with P. aeruginosa BSI over the 2-year study period; 40 cases with MDR P. aeruginosa and 66 cases with non-MDR P. aeruginosa were compared to 212 controls. Independent risk factors for the isolation of MDR P. aeruginosa were: presence of central venous catheter (CVC), previous antibiotic therapy, and corticosteroid therapy. Independent risk factors for non-MDR P. aeruginosa were: previous BSI, neutrophil count <500/mm3, urinary catheterization, and presence of CVC. The 21-day mortality rate of all patients was 33·9%. The variables independently associated with 21-day mortality were presentation with septic shock, infection due to MDR P. aeruginosa, and inadequate initial antimicrobial therapy.