Concepció Figueras

Prospective study of renal function in HIV-infected pediatric patients receiving tenofovir-containing HAART regimens

Aim:To describe the impact of tenofovir disoproxil fumarate (TDF) use on renal function in HIV-infected pediatric patients. Design:It is a prospective, multicenter study. The setting consisted of five third-level pediatric hospitals in Spain. The study was conducted on patients aged 18 years and younger who had received TDF for at least 6 months. The intervention was based on the study of renal function parameters by urine and serum analyses. The main outcome measures were renal function results following at least 6 months of TDF therapy. Results:Forty patients were included (32 were white and 26 were diagnosed with AIDS). Median (range) duration of TDF treatment was 77 months (16–143). There were no significant changes in the estimated creatinine clearance. Urine osmolality was abnormal in eight of 37 patients, a decrease in tubular phosphate absorption was documented in 28 of 38 patients, and 33 of 37 patients had proteinuria. A statistically significant decrease in serum phosphate and potassium concentrations was observed during treatment (P = 0.005 and P = 0.003, respectively), as well as a significant relationship between final phosphate concentration and tubular phosphate absorption (P = 0.010). A negative correlation was found between phosphate concentration and time on TDF. Conclusions:TDF use showed a significant association with renal tubular dysfunction in HIV-infected pediatric patients. Periodic assessment of tubular function may be advisable in the follow-up of this population.

Infecciones por Staphylococcus aureus resistente a meticilina adquirido en la comunidad en niños

INTRODUCTION Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections were first reported in the 1990s. Young, healthy individuals are frequently affected. The incidence of CA-MRSA in Spain is increasing. METHODS All children seen between August 2006 and January 2009 with CA-MRSA infections were included. The S. aureus isolates were studied by conventional techniques, their antibiotic susceptibility by agar disk diffusion, the presence of mecA gene was detected by multiplex polymerase chain reaction (PCR) and the gene encoding the Panton-Valentine leukocidin (PVL) by conventional PCR. CA-MRSA colonization was studied both in patients and their family members. RESULTS CA-MRSA was isolated in 15 samples from 12 patients, aged between 6 days and 14 years. Half of them were not native. Eight patients required hospital admission. The most common clinical presentation was skin and soft tissue infection (92%). Secondary CA-MRSA bacteraemia was present in two patients. All strains were PVL producers and two were resistant to macrolides associated to methicillin resistance and one of them was also resistant to lincosamides. An intra-familial transmission was identified. The clinical outcome was favourable in all patients. CONCLUSION CA-MRSA infections are emerging in Spain. Empirical treatment of skin and soft tissue infections should not be changed, since their incidence is still low. The drainage of CA-MRSA suppurative infections plays an important role in their treatment. Clindamycin or trimethoprim-sulfamethoxazole should be used for mild or moderate skin and soft tissue infections. Controlling the spread of these strains presents a challenge in the community today.

Intravenous and Subcutaneous Immunoglobulin Replacement: A Two-Way Road. Optimizing Healthcare Quality in Patients with Primary Immunodeficiencies

PurposeTo evaluate the alternate use of subcutaneous immunoglobulin (SCIG) and intravenous immunoglobulin (IVIG) in patients with primary immunodeficiencies (PID) in a third-level Pediatric University Hospital.MethodsRetrospective study of all patients receiving SCIG from 2006 to 2012. Data collected included demographics, date SCIG was started, date of switch to IVIG and reasons, administration tolerance, and related adverse events. Effectiveness was defined as the lack of severe infections.ResultsTwenty-three patients (15 male, 8 female) with PID were studied. SCIG was initiated at a median age of 14.2 years (8.4 months-25.7 years) and median duration on SCIG treatment was 41 months (4-68). Nine patients (39.1%) temporarily switched from SCIG to IVIG for the following reasons: vacation (8), administration issues (1), and transient need for immunomodulatory therapy (1). A mean of 5.2 IVIG infusions/patient (SD=2.86) was administered while on SCIG. IVIG-related adverse events were documented in 3 patients with 6 infusions. Eight (34.8%) patients definitively discontinued SCIG use for the following reasons: convenience (5), adverse effects (1), coagulopathy (1), and autoimmune thrombocytopenia (1). There were no severe infections requiring hospital admission in any patient during the study period.ConclusionsAlternating SCIG and IVIG use in patients with PID was associated with considerable advantages in terms of convenience for the patients and their caregivers, while maintaining the effectiveness and safety of this therapy. Healthcare units treating these patients should show flexibility with this dual therapy in order to optimize patients’ quality of life.

Adiponectin, Leptin and Inflammatory Markers in HIV-Associated Metabolic Syndrome in Children and Adolescents.

Background: Metabolic syndrome (MetS) is more common in HIV-infected adults and children than in the general population. Adipocytokines and inflammatory markers may contribute to the pathophysiology of this condition and could be useful indices for monitoring MetS. The objective of this study was to provide information on the prevalence of MetS and investigate the role of adipocytokines and other biomarkers in this syndrome in HIV-infected pediatric patients. Methods: A cross-sectional study was conducted between October 2013 and March 2014 in the outpatient clinics of 2 tertiary pediatric referral hospitals. Fifty-four HIV-infected children and adolescents were included. MetS was defined according to the International Diabetes Federation and modified National Cholesterol Education Program Adult Treatment Panel III criteria. Measurements included anthropometry, waist circumference, blood pressure, fasting lipids, glucose and insulin, adiponectin, leptin, interleukin-6, vitamin D and C-reactive protein and clinical lipodystrophy assessment. Results: Among the total, 3.7% of patients met the International Diabetes Federation criteria for MetS and 7.4% met the National Cholesterol Education Program Adult Treatment Panel III criteria. C-reactive protein and leptin levels were significantly higher and adiponectin level significantly lower in patients with MetS, regardless of the criteria used. Insulin resistance was observed in 40.7% of patients; abnormal quantitative insulin sensitivity check index values were found in 88.9%. Eighteen patients (33.3%) had vitamin D deficiency. Conclusions: The prevalence of MetS was similar to that observed in larger cohorts of HIV-infected patients in our setting. Adipocytokine dysregulation seems to be related to MetS in HIV-infected children. A high percentage of patients showed insulin resistance, which should be strictly monitored.

Indicadores de calidad asistencial para la atención de personas que viven con el virus de la inmunodeficiencia humana, adaptados a la edad pediátrica

INTRODUCTION Since infection with human immunodeficiency virus (HIV) was first described, there have been many advances in its diagnosis, monitoring and treatment. However, few contributions are related to the area of health care quality. In this sense, the Spanish Study Group on AIDS (GESIDA) has developed a set of quality care indicators for adult patients living with HIV infection that includes a total of 66 indicators, 22 of which are considered to be relevant. Standards were calculated for each of them in order to reflect the level of the quality of care offered to these patients. Similar documents for pediatric patients are currently lacking. METHODS Preparation of a set of quality care indicators applicable to pediatric patients based on the GESIDA document and the Spanish Guidelines for monitoring of pediatric patients infected with HIV. Each indicator was analysed with respect to the required standards in all patients under 18 years of age followed-up in our Unit, with the aim of evaluating the quality of care provided. RESULTS A total of 61 indicators were collected (51 from the GESIDA document and 10 from currently available pediatric guidelines), 30 of which were considered to be relevant. An overall compliance of 81%-83% was obtained when assessing the relevant indicators. CONCLUSION The availability of health care quality standards is essential for the care of pediatric HIV-infected patients. The assessment of these indicators in our Unit yielded satisfactory results.

PO-0260d The Usefulness Of An Antimicrobial Stewardship Program: Eight-year Trends Of Anti-infective Therapy In A Tertiary Paediatric Hospital From Barcelona

Background and aims Antimicrobial drug resistance is a serious threat to public health worldwide. Antimicrobial stewardship program (ASP) information related to the paediatric population is scarce. This study assesses the usefulness of ASP instituted in 2005 in our centre. Methods Retrospective study in a 214 bed-tertiary care paediatric hospital (52% patients in high-complexity areas), from 2005 to 2012. Variation in admissions, hospital complexity index, mortality rate, bacterial resistance and invasive fungal filamentous infection (IFFI) episodes were recorded. Rates of systemic antibiotics (glycopeptides, aminoglycosides, carbapenems) and intravenous antifungal drugs consumption in admitted patients were assessed, calculated by drug units and related cost. Results A significant decrease in the number of admissions (-27%) was observe but complexity index and number of transplants increased significantly (+206% and +14%, respectively), as episodes of proven and probable IFFI (+88%). ESBL E.coli and K.pneumoniae increased (5 to 7.6% and 13.8 to 20%) while AmpC hiperproduced Enterobacter cloacae remained stable (29.2 to 29.5%). Multiresistant P. aeruginosa (1.1 to 5%) and MRSA (6.5 to 12.2%) increased moderatelely. Mortality rate showed a decrease of 8%. The use of aminoglycosides (-24%) and glycopeptides (-3%) decreased while carbapenem and antifungal drug use increased (+45 and +76%, respectively) less than complexity indicators along these years. Global antimicrobial cost slightly increased (+14%). Conclusions Since ASP implementation a considerable proportional decrease in anti-infective drugs use in comparison to complexity indexes and severe infection episodes was observed without an increase in mortality. ASP should be implemented in all high-complexity paediatric hospitals to optimise patient’s care.

Severely immunocompromised HIV-infected paediatric patient with drug-resistant cytomegalovirus infection treated with subcutaneous interleukin-2

Several studies have demonstrated substantial expansion of CD4 T cells in adult and paediatric HIV-infected patients treated with interleukin-2 (IL-2). None of these studies have included patients with other active infections; hence, the infection reactivation risk in patients receiving IL-2 remains unknown. We report the case of a 14-year-old HIV-infected boy with AIDS-associated wasting syndrome, severe malnutrition (height and weight at -6 SD below ageand sex-adjusted mean) and cytomegalovirus (CMV) disease with pulmonary and retinal involvement, under treatment with intravenous ganciclovir and foscarnet. Genotype resistance testing performed 1 year before starting IL-2 showed multiple mutations in the reverse transcriptase (M41L, D67N, K101E, V118I), protease (L10I, L33V, M46I, L63P, A71V, V82F, L90M) and envelope gene associated with resistance to entry inhibitors (V38M, N43D). Therefore, treatment with boosted darunavir and etravirine (dose-adjusted by pharmacokinetic studies) was started at that time. The patient presented undetectable HIV viral load 2 months after beginning this new regimen, but immunological restoration was never achieved. At that point, in addition to antiviral therapy, treatment with subcutaneous IL-2 (Proleukin, Novartis Pharmaceuticals Ltd., West Sussex, UK) at a dose of 4 MU/m given twice daily in 5-day courses every 8 weeks for 6 cycles was started, after obtaining authorisation for compassionate use by the Spanish Agency for Medicines and Healthcare Products (AEMPS). HIV viral load remained undetectable and CD4 cell count was 6% (105 cells/ mm). CMV viral load was 84 000 copies/mL at that time. During this period, HIV viral load remained undetectable and CD4 cell count exhibited a significant 11% increase (258 cells/ mm) 15 days after initiating therapy (Fig. 1). At the end of the first cycle, the patient presented capillary leak syndrome resulting in multiple organ failure (renal and respiratory failure, and hypotension), and CMV exacerbation in both the intestine and retina. He was admitted to the Paediatric Intensive Care Unit for 1 week, with progressive stabilisation. Due to these severe late-onset adverse reactions, IL-2 therapy was definitely discontinued. In the following month, CMV viral load increased 27-fold (from 84 000 to 6 130 037 copies/mL). Intestinal CMV progression resulted in uncontrolled rectorrhagia that led to the patient’s death 34 days after starting IL-2. This adverse reaction was reported to the spontaneous notification programme for adverse drug reactions and the AEMPS. Resistance to both ganciclovir and foscarnet was demonstrated after the patient’s death (M460V and K513R). IL-2 is a cytokine produced by T lymphocytes that promote lymphocyte proliferation and differentiation of CD4 and CD8 T cells. Several phase I/II clinical studies have demonstrated that intermittent subcutaneous or continuous intravenous administration of IL-2 in HIV-infected patients induces substantial expansion of CD4 T cells, as observed in our patient. These studies recommend the intermittent subcutaneous route to minimize drug-associated side effects. A major concern regarding the use of IL-2 is the theoretical risk that this cytokine could stimulate HIV replication, although this did not happen in our patient. Although drug-related toxicities are described as common in most clinical trials, these events are limited to the period of drug administration and are resolved at the end of the cycle. In a paediatric series, more than 90% had fatigue, malaise or lethargy during the IL-2 administration cycle. Other common adverse events include headache or myalgia (66%); pruritis, generalized rash or urticaria (75%); nausea, emesis, anorexia and diarrhoea (83%); respiratory symptoms (33%); and oedema (25%). No severe adverse reactions such as those occurring in our patient have been reported. Capillary leak syndrome has been described as an adverse reaction associated with IL-2 administration. However, it usually appears shortly after initiation of therapy and is reported to be less severe with subcutaneous route. As to CMV exacerbation with the use of IL-2, this effect has not been described as such in the literature. Nevertheless, it should be mentioned that IL-2 use is contraindicated in patients with evidence of active infection. The decision to initiate IL-2 therapy in our patient was based on his critical status and the fact that CMV infection was partially controlled with intravenous antiviral therapy. In addition, according to Yu et al., the use of IL-2 restores the proliferative response of CMV-specific CD8+ T cells in patients with HIV. Despite subcutaneous IL-2 seems useful in increasing CD4 counts even in severely immunocompromised HIV-infected paediatric patients with concomitant uncontrolled infections, 0 100 200 300 400 500 600 700