Factors associated with sepsis development in 606 Spanish adult patients with cellulitis.

BACKGROUND: Cellulitis, a frequent cause of admission of adult patients to medical wards, occasionally evolves to sepsis. In this study we analyze the factors related to sepsis development. METHODS: Prospective and observational study of 606 adult patients with cellulitis admitted to several Spanish hospitals. Comorbidities, microbiological, clinical, lab, diagnostic, and treatment data were analyzed. Sepsis was diagnosed according to the criteria of the 2016 International Sepsis Definitions Conference. Multiple logistic regression modelling was performed to determine the variables independently associated with sepsis development. RESULTS: Mean age was 63.4 years and 51.8% were men. Overall 65 (10.7%) patients developed sepsis, 7 (10.8%) of whom died, but only 4 (6.2%) due to cellulitis. Drawing of blood (P < 0.0001) or any (P < 0.0001) culture, and identification of the agent (P = 0.005) were more likely among patients with sepsis. These patients had also a longer duration of symptoms (P = 0.04), higher temperature (P = 0.03), more extensive cellulitis (P = 0.02), higher leukocyte (P < 0.0001) and neutrophil (P < 0.0001) counts, serum creatinine (P = 0.001), and CRP (P = 0.008) than patients without sepsis. Regarding therapy, patients with sepsis were more likely to undergo changes in the initial antimicrobial regimen (P < 0.0001), received more antimicrobials (P < 0.0001), received longer intravenous treatment (P = 0.03), and underwent surgery more commonly (P = 0.01) than patients without sepsis. Leukocyte counts (P = 0.002), serum creatinine (P = 0.003), drawing of blood cultures (P = 0.004), change of the initial antimicrobial regimen (P = 0.007) and length of cellulitis (P = 0.009) were independently associated with sepsis development in the multivariate analysis. CONCLUSIONS: Increased blood leukocytes and serum creatinine, blood culture drawn, modification of the initial antimicrobial regimen, and maximum length of cellulitis were associated with sepsis in these patients.

Factors associated with development of nephrotoxicity in patients treated with vancomycin versus daptomycin for severe Gram-positive infections: A practice-based study.

OBJECTIVE: To evaluate nephrotoxicity development in patients treated with vancomycin (VAN) and daptomycin (DAP) for proven severe Gram-positive infections in daily practice. METHODS: A practice-based, observational, retrospective study (eight Spanish hospitals) was performed including patients ≥18 years with a baseline glomerular filtration rate (GFR)>30 mL/min and/or serum creatinine level<2 mg/dL treated with DAP or VAN for >48h. Nephrotoxicity was considered as a decrease in baseline GRF to <50 mL/min or decrease of >10 mL/min from a baseline GRF<50 mL/min. Multivariate analyses were performed to determine factors associated with 1) treatment selection, 2) nephrotoxicity development, and 3) nephrotoxicity development within each antibiotic group. RESULTS: A total of 133 patients (62 treated with DAP, 71 with VAN) were included. Twenty-one (15.8%) developed nephrotoxicity: 4/62 (6.3%) patients with DAP and 17/71 (23.3%) with VAN (p=0.006). No differences in concomitant administration of aminoglycosides or other potential nephrotoxic drugs were found between groups. Factors associated with DAP treatment were diabetes mellitus with organ lesion (OR=7.81, 95%CI:1.39-4.35) and basal creatinine ≥0.9 mg/dL (OR=2.53, 95%CI:1.15-4.35). Factors associated with VAN treatment were stroke (OR=7.22, 95%CI:1.50-34.67), acute myocardial infarction (OR=6.59, 95%CI:1.51-28.69) and primary bacteremia (OR=5.18, 95%CI:1.03-25.99). Factors associated with nephrotoxicity (R2=0.142; p=0.001) were creatinine clearance<80 mL/min (OR=9.22, 95%CI:1.98-30.93) and VAN treatment (OR=6.07, 95%CI:1.86-19.93). Factors associated with nephrotoxicity within patients treated with VAN (R2=0.232; p=0.018) were congestive heart failure (OR=4.35, 95%CI:1.23-15.37), endocarditis (OR=7.63, 95%CI:1.02-57.31) and basal creatinine clearance<80 mL/min (OR=7.73, 95%CI:1.20-49.71). CONCLUSIONS: Nephrotoxicity with VAN was significantly higher than with DAP despite poorer basal renal status in the DAP group.

Genotypic tropism testing of proviral DNA to guide maraviroc initiation in aviraemic subjects: 48-week analysis of results from the PROTEST study.

OBJECTIVES: Maraviroc (MVC) is a suitable drug for aviraemic subjects on antiretroviral treatment (ART) developing toxicity. Its prescription requires prior tropism testing. It is unknown if proviral DNA genotypic tropism testing is reliable for guiding MVC initiation in aviraemic subjects, so this study was carried out to address this issue. METHODS: PROTEST was a phase 4, prospective, single-arm clinical trial carried out in 24 HIV care centres in Spain. MVC-naïve HIV-1-infected patients with HIV-1 RNA < 50 copies/mL on stable ART during the previous 6 months who required an ART change because of toxicity and who had R5 HIV, as determined by proviral DNA genotypic tropism testing, initiated MVC with two nucleoside reverse transcriptase inhibitors (NRTIs) and were followed for 48 weeks. Virological failure was defined as two consecutive viral load measurements > 50 copies/mL. RESULTS: Tropism results were available for 141 of 175 (80.6%) subjects screened: 60% had R5 and 85% of these (n = 74) were finally included in the study. Previous ART included protease inhibitors (PIs) in 62% of subjects, nonnucleoside reverse transcriptase inhibitors (NNRTIs) in 36%, and integrase inhibitors (INIs) in 2%. Main reasons for treatment change were dyslipidaemia (42%), gastrointestinal symptoms (22%) and liver toxicity (15%). MVC was given alongside tenofovir (TDF)/emtricitabine (FTC) (54%) and abacavir (ABC)/lamivudine (3TC) (40%) in most patients. Eighty-four per cent of patients maintained a viral load < 50 copies/mL to week 48, whereas 16% discontinued treatment: two withdrew informed consent, one had an R5 to X4 shift between screening and baseline, one was lost to follow-up, one developed an adverse event (rash), two died from non-study-related causes, and five developed protocol-defined virological failure. CONCLUSIONS: Initiation of MVC plus two NRTIs in aviraemic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure for up to 1 year.

Impact of nosocomial polymicrobial bloodstream infections on the outcome in critically ill patients.

The aims of this study were to compare the clinical and microbiological characteristics from patients with polymicrobial bloodstream infections (BSI) to those from patients with monomicrobial BSI and to determine their influence on the prognosis. A prospective study was conducted on 371 nosocomial BSI in an intensive care unit (ICU). Seventy-five (20.2%) of them were polymicrobial. The mean APACHE II score at the onset of bacteremia in polymicrobial and monomicrobial BSI were 17.7 ± 6.6 and 18.9 ± 7.5, respectively (p=0.228). Severe sepsis and septic shock were present in 68.0% and 50.6% of polymicrobial BSI and in 73.9% and 55.1% of monomicrobial BSI, respectively (p=0.298 and p=0.494, respectively). The length of stay and the length of stay post-infection were significantly longer in patients with polymicrobial BSI. APACHE II score at the onset of BSI, high-risk microorganisms, and septic shock were predictors of related mortality, but polymicrobial BSI and inadequate empirical antimicrobial treatment were not. Our findings suggest that the clinical and microbiological characteristics of polymicrobial BSI are not different from monomicrobial BSI, and polymicrobial BSI do not have any influence on the related mortality. However, they occurred in patients with a longer length of stay in the hospital and were associated with longer stays in the hospital after the episode of BSI.

[A descriptive study of perinatal asphyxia and its sequelae]. / Estudio descriptivo de la asfixia perinatal y sus secuelas.

INTRODUCTION: Perinatal asphyxia is a potential cause of brain injury that can produce some alterations on the neurologic development of the newborn. On the last years most part of the investigation have been focused on the physiopathology of the perinatal asphyxia, but correlation between asphyxia and brain damage is not well defined. PATIENTS AND METHODS: A retrospective study was made of the patients with the diagnosis of perinatal asphyxia born at the General Hospital of Segovia during a period of ten years (1992-2001). We took data about gestation, birth, neonatal period and follow-up period from their clinical histories. RESULTS: Over this period of ten years 703 cases of perinatal asphyxia have been diagnosed, supposing this an incidence of 7,2 cases of each 100 newborns. 116 of these newborns present risk factors of brain damage and were followed at least two years. 53 of the 116 newborns (45%) present evidence of hypoxic-ischemic encephalopathy on neonatal period. During the period of two years, 42 of the asphyxiated infants follow up (36%) present neurologic sequelae, being psychomotor retardation the most common. CONCLUSION: For a correct interpretation of the relationship between perinatal asphyxia and neurologic sequelae we have to analyze all of the perinatal data and discard any other possible aetiology or pathogenic mechanism.

The influence of inadequate empirical antimicrobial treatment on patients with bloodstream infections in an intensive care unit.

OBJECTIVE: To determine the occurrence of inadequate antimicrobial therapy among critically ill patients with bacteremia and the factors associated with it, to identify the microorganisms that received inadequate antimicrobial treatment, and to determine the relationship between inadequate treatment and patients outcome. METHODS: From June 1995 to January 1999 we collected data on all clinically significant ICU-bacteremias in our teaching hospital. Clinical and microbiological characteristics were recorded and the adequacy of empirical antimicrobial treatment in each case was determined. We defined inappropriate empirical antimicrobial treatment as applying to infection that was not being effectively treated at the time the causative microorganism and its antibiotic susceptibility were known. Multivariate analysis was used to determine the variables associated with inappropriate empirical antimicrobial treatment and to evaluate the influence of this on the related mortality to bacteremia, using the SPSS package (9.0). RESULTS: Among 166 intensive care unit patients with bacteremia, 39 (23.5%) received inadequate antimicrobial treatment. In this last group the mean age of patients was 64.1 +/- 13.2 years, and 64% were men. Bacteremia was hospital-acquired in 92% of these cases. Eleven percent developed septic shock and 37.7% severe sepsis, and ultimately fatal underlying disease was present in 28.2% of patients given inadequate empirical antimicrobial treatment. The main sources of bacteremias in this group were: a vascular catheter (15.3%), respiratory (7.6%) or unknown (53.8%). The microorganisms most frequently isolated in the group with inadequate empirical antimicrobial treatment were: coagulase-negative staphylococci (29.5%), Acinetobacter baumannii (27.3%), Enterococcus faecalis, Pseudomonas aeruginosa, Enterobacter cloacae, Proteus mirabilis, Escherichia coli, and Candida species (4.5% each). The frequency of coagulase-negative staphylococci in the cases with inappropriate treatment was higher than in the group with appropriate treatment (OR 2.62; 95% CI: 1.10-6.21; P = 0.015). The global mortality rate was 56% and the related mortality was 30% in the group with inadequate empirical antimicrobial treatment. The only factor associated with inappropriate empirical antibiotic treatment was the absence of abdominal or respiratory focus (P = 0.04; OR = 0.35; 95% CI: 0.12-0.97). Septic shock was related to attributable mortality (P = 0.03; OR = 3.19; 95% CI: 1.08-9.40), but not inappropriate empirical antibiotic treatment (P = 0.24; OR = 1.71; 95% CI: 0.66-4.78). CONCLUSION: Almost a quarter of critically ill patients with bloodstream infections were given inadequate empirical antibiotic treatment, but mortality was not higher in the group with inadequate treatment than in the group with adequate treatment. This fact was probably due to microbiological factors and clinical features, such as the type of microorganism most frequently isolated and the source of the bacteremia.

[Neonatal onset methylmalonic aciduria and homocystinuria:Biochemical and clinical improvement with betaine therapy]. / Aciduria metilmalónica con homocistinuria de inicio neonatal: mejoría bioquímica y clínica con betaína.

Methylmalonic aciduria and homocystinuria is a very rare inborn error of cellular cobalamin (Cbl) metabolism. We describe the biochemical evolution and clinical course of a boy with neonatal onset CblC mutant defect.Born after a normal pregnancy, the patient developed general hypotonia and severe feeding difficulties at 5 days of life. Diagnosis of methylmalonic aciduria and homocystinuria was established by amino-acid and organic acid analysis and was confirmed by enzyme and genetic studies. The patient was initially treated with parenteral hydroxocobalamin (1 mg/day), oral carnitine (100 mg/kg/day) and a restricted protein diet. This treatment returned methylmalonic acid levels to normal. Despite the parenteral hydroxocobalamin therapy, the patient showed no improvement in neurological dysfunction, hypotonia or developmental delay. Oral betaine supplementation (3 g/day) from months 3-15 reduced plasma total homocysteine and homocystinuria. The patient showed clinical improvement in neurological and growth development. We conclude that early betaine therapy was safe and effective in our patient with neonatal onset methylmalonic aciduria and homocystinuria type CblC.

[Accidental oral mercurochrome poisoning]. / Intoxicación oral accidental por mercurocromo.

Neonatal mercury poisoning, especially that due to merbromin ingestion, is uncommon. We describe the case of a 10 day old newborn infant who was given mercurochrome orally for 7 days due to misunderstanding of medical instructions. Initial symptoms included loss of appetite and low weight increase. Elevated blood mercury concentrations were found. Chelating therapy with dimercaprol was initiated and the patient's evolution was good. We discuss the potential toxicity of mercury and emphasise the importance of the transmission of information by physicians, especially to the immigrant population.

[Practice variation and appropriateness study of antimicrobial therapy for acute pharyngotonsillitis in adults]. / Variabilidad e idoneidad de la prescripción antibiótica en faringoamigdalitis agudas del adulto.

OBJECTIVE: Infectious pharyngotonsillitis is usually managed with antibiotics by general practitioners and pediatricians both in primary care and the emergency services. In the present work we try to assess the antibiotic variability and appropriateness in the management of acute pharyngotonsillitis among several emergency services in our country related to scientific evidence based in an expert panel criteria. METHOD: A transversal trial was carried on in ten emergency services of our country. We included patients older than fourteen years an analyzed the following variables: type of respiratory infection, antibiotic prescription, comorbidity, physician's status and hospital admission. The antibiotics were classified in three levels according to the expert panel criteria: first election, alternative use and inappropriate use. We compared the antibiotic treatments to these three levels. RESULTS: 2,869 patients were diagnosed of acute respiratory infection, 356 (12.4%) with pharyngotonsillitis. Commonly the patients were prescribed antibiotics (315; 81%) and the most used were amoxicillin-clavulanate (33%), amoxicillin (16%), penicillin (7%), cefuroxime (6%), erythromicin (4%) and cefixime (3%). Among the 315 prescriptions, 98 (32%) were first election, 147 (50%) alternative use and 50 (17%) inappropriate use. CONCLUSIONS: Most of the patients suffering of pharyngotonsillitis were empirically prescribed antibiotics probably many of these cases were non-bacterial pharyngotonsillitis. Alternative and inappropriate use of antibiotics was high.

[Multicenter study of the variability and adequacy of antimicrobial therapy for community-acquired pneumonia in adults] / Estudio multicéntrico de variabilidad e idoneidad de la prescripción antibiótica en la neumonía adquirida en la comunidad del adulto.

We performed a study to evaluate the variability and adequacy of prescribing antibiotics in community-acquired pneumonia (CAP) in 10 Spanish hospitals. We studied 452 patients with CAP. Initial empirical administration of antibiotics was prescribed in 90.7% of the cases, 82.5% as monotherapy. Macrolides and third and second generation cephalosporins were the most widely used groups of antibiotics. Penicillin and amoxicillin were only prescribed in 1.7% of the patients. A significant variability between hospitals was observed. Reference patterns for the use of antibiotics in CAP were devised by a panel of experts. According to the recommendations of this panel, 29% of the total prescriptions were not adequate, with this percentage reaching 65% in outpatients older than 65 years or with comorbidity. This was mainly due to the fact that monotherapy with erythromycin, which was considered inadequate, was the most widely prescribed treatment.

[Multicenter study of the variability and adequacy of antimicrobial therapy for community-acquired pneumonia in adults]. / Estudio multicéntrico de variabilidad e idoneidad de la prescripción antibiótica en la neumonía adquirida en la comunidad del adulto.

We performed a study to evaluate the variability and adequacy of prescribing antibiotics in community-acquired pneumonia (CAP) in 10 Spanish hospitals. We studied 452 patients with CAP. Initial empirical administration of antibiotics was prescribed in 90.7% of the cases, 82.5% as monotherapy. Macrolides and third and second generation cephalosporins were the most widely used groups of antibiotics. Penicillin and amoxicillin were only prescribed in 1. 7% of the patients. A significant variability between hospitals was observed. Reference patterns for the use of antibiotics in CAP were devised by a panel of experts. According to the recommendations of this panel, 29% of the total prescriptions were not adequate, with this percentage reaching 65% in outpatients older than 65 years or with comorbidity. This was mainly due to the fact that monotherapy with erythromycin, which was considered inadequate, was the most widely prescribed treatment.

[Tuberculosis in AIDS patients: the contribution of an analysis of the restriction fragment length polymorphism of Mycobacterium tuberculosis isolates]. / Tuberculosis en pacientes con SIDA: aportación del análisis de los fragmentos de restricción de longitud polimórfica aislados de Mycobacterium tuberculosis.

BACKGROUND: In this report we study tuberculosis transmission in HIV infected patients using molecular epidemiological methods. PATIENTS AND METHODS: We have studied 60 M. tuberculosis isolates from 30 HIV infected cases, and their clinical-epidemiological data. Susceptibility to tuberculostatic agents and electrophoretic patterns using RFLPs (restriction fragment length polymorphisms) method were evaluated. Dice's coefficient was used for the similarity analysis. RESULTS: Over 73% studied patients were included in clusters using RFLPs analysis. This data show that nearly 60% of the tuberculosis cases in our area have a recent transmission. Forty per cent of these cases were included in the main cluster. The frequency of tuberculostatic-resistant strains in HIV infected patients was similar to the that of observed in other patients. We did not find correlation between RFLPs clusters and clinical-epidemiological data. CONCLUSIONS: Tuberculosis transmission in HIV-positive patients using RFLPs as molecular marker shows that 60% of the cases are caused by recently acquired strains. We did not find multi-drug resistant strains in our isolates. However due to the high transmissibility of these circulating clones, control disease measures in this group of risk population are required.

[A comparison of lymphocyte populations of the blood and bronchoalveolar lavage in AIDS patients]. / Comparación de poblaciones linfocitarias de sangre y lavado broncoalveolar en pacientes con SIDA.

Changes in cell immunity made manifest by decreases in blood levels of CD4 T cells is the main indicator of progressing HIV infection. The decrease in these lymphocytes, as well as in the CD4/CD8 index and increases in suppressant or cytotoxic CD8 cells can be detected in bronchoalveolar (BAL) lung samples. It is not clear whether the high incidence of respiratory system diseases in HIV patients stems from local or systemic immune changes. The aim of this study was to compare changes in the systemic cell immunity studied in samples of peripheral blood with changes detected in BAL samples from HIV patients with acute respiratory disease. We studied 42 patients in the advanced stages of AIDS (C3 by Centers for Disease Control classification) who were hospitalized for acute respiratory disease and who underwent diagnostic fiberoptic bronchoscopy and BAL. Cell counts and lymphocyte populations were analyzed by flow cytometry in samples of peripheral blood and BAL. The percentage of CD4 lymphocytes and the CD4/CD8 index were lower in BAL, particularly in patients with blood CD4 levels below 12% of the total T cell population, or at a level of 20 CD4 cells/microliters. Changes in cell immunity in patients with advanced HIV infection (C3 classification) and acute respiratory disease are more manifest locally in the lung than peripherally in blood. Lung depletion of CD4 T cells in the lung can be predicted based on blood levels.

[Use of DNA amplification to diagnose cytomegalovirus in HIV seropositive patients]. / Utilidad de la amplificación de DNA para diagnosticar citomegalovirus en la población seropositiva para el virus de la inmunodeficiencia humana.

BACKGROUND: Cytomegalovirus (CMV) infection is common among HIV seropositive patients, being difficult to diagnose because it requires cell cultures not available in all hospitals. DNA amplification is being applied for diagnosis of infectious diseases with an increase in sensitivity and specificity with respect to previous laboratory methods. METHODS: Polymerase chain reaction (PCR) has been used in comparison with culture isolation, early antigen detection to diagnose CMV infection in 22 HIV infected patients, that suffered from symptoms compatible with CMV infection at the present time, and in other 5 patients suffering from Kaposi sarcoma. PCR was done with primer for CMV IE genomic region. The amplified sequences were detected after hybridization with a gamma-P-32 labelled probe, followed by electrophoresis in a 5% polyacrylamide gel and autoradiography. RESULTS: The PCR allows to detect CMV genome in cases in which other tests are negatives, in blood as well as in urine, included those patients suffering only from febrile symptoms or with other associated pathogen. CONCLUSIONS: PCR is a sensitive method to detect CMV, although it does not establish the responsibility of CMV in HIV infected patients.

Immune response to hepatitis B vaccine in parenteral drug abusers.

Responsiveness was assessed to a programme of vaccination of hepatitis B vaccine in a cohort of 197 intravenous drug addicts (mean age, 23.7 years) and their antibody response was compared with that of 271 healthy controls (mean age, 24.2 years). All participants were seronegative for hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). The vaccination schedule consisted of three intramuscular injections (deltoid area) at months 0, 1 and 2. Although 70% of parenteral drug abusers received the three doses of vaccination, only 43.6% were evaluable for immune response. Fifty-eight per cent of heroin addicts and 80% of controls had evidence of anti-HBs seroconversion at 1 month after vaccination (chi 2 = 15.52, p less than 0.001). Geometric mean antibody titres were also significantly higher in controls (69.1 IU l-1; confidence interval 95%, 56.83 and 84.04) than in parenteral drug abusers (18.2 IU l-1; confidence interval 95%, 12.85 and 25.73) (F = 20.951, p less than 0.0001). The anti-HBs response was not influenced by coexistent anti-HBc, HCV antibody or HIV antibody seropositivity.