Miguel Górgolas

Focal infections due to non-typhi Salmonella in patients with AIDS: report of 10 cases and review.

Bacteremia due to non-typhi Salmonella is frequent in human immunodeficiency virus (HIV)-infected patients; however, focal complications rarely have been reported. Ten of 38 HIV-infected patients (26.3%) with salmonellosis documented over a period of 9 years had focal suppurative complications; only 19 (3.9%) of 490 adults without HIV infection who were seen during the same period had focal complications (P = .001). Infections of the urinary tract, lungs, and soft tissue, followed by arthritis, endocarditis, and meningitis were most frequently seen. Although salmonellosis occasionally heralded HIV infection, most patients were severely immunocompromised and had CD4 cell counts of <100/mm3. The mortality rate was 50%, equivalent to that observed among patients with other immunosuppressive disorders (52.6%). Major emphasis must be put on intensive therapy for salmonella bacteremia and prevention of its complications.

Enterococcal endocarditis on native and prosthetic valves: a review of clinical and prognostic factors with emphasis on hospital-acquired infections as a major determinant of outcome.

Enterococci are the third leading cause of infectious endocarditis, and despite advances in diagnosis and treatment, the mortality of enterococcal endocarditis has not changed in recent decades. Although variables such as advanced age, cardiac failure, and brain emboli have been recognized as risk factors for mortality, cooperative multi-institutional studies have not assessed the role of other variables, such as nosocomial acquisition of infection, the presence of comorbidities, or the changing antimicrobial susceptibility of enterococci, as factors determining prognosis. We conducted the current study to determine the risk factors for mortality in patients with enterococcal endocarditis in a single institution. We reviewed 47 consecutive episodes of enterococcal endocarditis in 44 patients diagnosed according to the modified Duke criteria from a retrospective cohort study of cases of infectious endocarditis. The main outcome measure was inhospital mortality. We applied stepwise logistic regression analysis to identify risk factors for mortality. Predisposing heart conditions were observed in 86.3% of patients, and 17 had prosthetic valve endocarditis. A portal of entry was suspected or determined in 38.2%; the genitourinary tract was the most common source of the infection (29.7%). Comorbidities were present in 52.2% of cases. Twelve episodes (25.5%) were acquired during hospitalization. Only 3 isolates of Enterococcus faecalis were highly resistant to gentamicin. Eighteen patients (40.9%) needed valve replacement due to cardiac failure or relapse. Comparing cases of native valve and prosthetic valve endocarditis, we found no differences regarding complications, the need for surgical treatment, or mortality. Eight of 44 (18%) episodes were fatal. Age over 70 years (p = 0.05), heart failure (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.15-2.25; p = 0.001), presence of 1 or more comorbidities (OR, 3.2; 95% CI, 1.11-9.39; p = 0.02), and nosocomial acquisition (OR, 8.05; 95% CI, 1.50-43.2; p = 0.01) were associated with mortality. In the multivariate analysis, only nosocomial acquisition increased the risk of mortality. In patients with enterococcal endocarditis, nosocomial acquisition of infection is an important factor determining outcome. As the incidence of bacteremia and the population of elderly people at risk continue to grow, the hazard of acquiring nosocomial enterococcal endocarditis may increase; hence, major emphasis must be put on prevention. Abbreviations: CT = computed tomography, HIV = human immunodeficiency virus, MIC = minimum inhibitory concentration, NVE = native valve endocarditis, PVE = prosthetic valve enterococcal endocarditis, TEE = transesophageal echocardiogram, TTE = transthoracic echocardiogram.

Endocarditis caused by Staphylococcus aureus: A reappraisal of the epidemiologic, clinical, and pathologic manifestations with analysis of factors determining outcome.

Staphylococcus aureus is the leading cause of infectious endocarditis and its mortality has remained high despite better diagnostic and therapeutic procedures over time. We conducted a retrospective review of 133 cases of definite S. aureus endocarditis seen at a single tertiary care hospital over 22 years to assess changes in the epidemiology and incidence of the infection, manifestations, outcome, risk factors for mortality, and impact of cardiac surgery on prognosis. Patients were classified into 2 groups: 1) right-sided endocarditis (64 patients) and 2) left-sided endocarditis (69 patients). While the number of cases of left-sided endocarditis remained steady at 1-3 cases per 10,000 admissions, the incidence of right-sided endocarditis, after a peak in the early 1990s, declined to almost disappear in 2001. Among the cases of right-sided endocarditis, we found 2 subsets of patients with different clinical features and prognosis: the first subset comprised 53 intravenous drug abusers, and the second subset comprised 11 patients with catheter-associated S. aureus bacteremia and endocarditis. Fifty-one patients were human immunodeficiency virus (HIV)-positive drug abusers, most of whom (80.3%) had right-sided endocarditis. We did not find differences in mortality between HIV-positive and HIV-negative individuals; mortality seemed to depend more on the site of the heart involved than on HIV status. Among the cases of left-sided endocarditis, the mitral valve was more commonly involved than the aortic valve (61% vs. 30%). Overall, 74% of patients with left-sided endocarditis developed 1 or more cardiac or extracardiac complication. In comparison, only 23.4% of patients with right-sided endocarditis developed complications. Prosthetic valve endocarditis (PVE) was hospital-acquired more frequently than native valve endocarditis (NVE). Patients with PVE had a shorter duration of symptoms until diagnosis and presented with or developed cardiac murmurs less frequently than patients with NVE. Cardiac failure (49%), renal failure (43%) and central nervous system (CNS) events (35%) were frequently observed in patients with both PVE and NVE. Valve replacement was more frequently needed and more rapidly performed in patients with PVE than in their counterparts with NVE. The overall mortality of patients with right-sided endocarditis was 17%. While the mortality of right-sided endocarditis in injection drug users was 3.7%, the mortality of patients with right-sided endocarditis associated with infected intravenous catheters was 82% (odds ratio [OR], 0.01; 95% confidence interval [CI], 0.001-0.07). For left-sided endocarditis mortality was 38% and was not significantly different in patients with NVE or PVE (OR, 0.65; 95% CI, 0.23-1.87). CNS complications were associated with mortality in both NVE (OR, 6.55; 95% CI, 1.78-24.04) and PVE (OR, 32; 95% CI, 2.63-465.40). Development of 2 or 3 complications was associated with an increased risk of mortality (OR, 5.59; 95% CI, 1.08-28.80 and OR, 9.25; 95% CI, 1.36-62.72 for 2 vs. 1 complication and for 3 vs. 2 complications, respectively). Surgical treatment did not significantly influence mortality in cases of NVE, (OR, 3.19; 95% CI, 0.76-13.38) but significantly improved the prognosis of patients with PVE (OR, 69; 95% CI, 2.89-1647.18). S. aureus endocarditis is an aggressive, often fatal, infection. The results of the current study suggest that valve replacement will improve the outcome of infection, particularly in patients with PVE. Abbreviations: AIDS = acquired immunodeficiency syndrome, CI = confidence interval, CNS = central nervous system, HIV = human immunodeficiency virus, MIC = minimum inhibitory concentration, MRSA = methicillin-resistant Staphylococcus aureus, MSSA = methicillin-susceptible Staphylococcus aureus, NVE = native valve endocarditis, OR = odds ratio, PVE = prosthetic valve endocarditis, TEE = transesophageal echocardiogram, TTE = transthoracic echocardiogram.

Factors Determining Serologic Response to Treatment in Patients with Syphilis

BACKGROUND The goal of this study was to describe the clinical and epidemiologic manifestations of a syphilis outbreak in downtown Madrid, Spain. Because human immunodeficiency virus (HIV)-positive patients may be at increased risk of serologic failure during syphilis treatment, analysis of factors determining the response to treatment was performed in a cohort of HIV-positive and HIV-negative patients with syphilis. METHODS We performed a longitudinal, retrospective study of patients with syphilis who received the diagnosis at a university-affiliated hospital in Madrid from 2003 through 2007. RESULTS Three hundred forty-seven cases of syphilis were identified and treated (30 primary, 164 secondary, 77 early latent, and 76 late cases of syphilis). Forty-one percent of patients were immigrants, mostly from South America and the Caribbean, and 49.3% were known to be HIV positive. Syphilis incidence increased from 15.6 to 35 cases per 100,000 person-years from 2003 to 2007. Most patients were men, and 50.4% were men who had sex with other men. Meningitis (4.9%) and uveitis (2.9%) were the complications most frequently observed, and their frequency did not differ between HIV-positive and HIV-negative patients. Serologic failure was observed in 44 (23.5%) patients: 37 (29.6%) of 125 HIV-positive patients and 7 (11.2%) of 62 HIV-negative patients (odds ratio, 3.3; 95% confidence interval, 1.38-7.93; P < .05). Men (hazard ratio [HR], 0.38), patients in the late stage of syphilis (HR, 0.46), and HIV-positive persons (HR, 0.61) demonstrated slower serological responses to treatment. HIV-negative patients responded more frequently to treatment, but after 2 years of follow-up, both groups shared similar response rates. Antiretroviral treatment reduced the time to serologic response (HR, 2.08; 95% confidence interval, 1.35- 3.20; P < .001). CONCLUSION Syphilis incidence rose 223% from 2003 to 2007, affecting mostly HIV-positive men, men who have sex with men, and immigrants. Men, patients in the late stages of syphilis, and HIV-positive persons may be at increased risk of serologic failure. Antiretroviral therapy significantly reduced the time to achieve response to syphilis treatment in HIV-positive patients.

Evolution of bone mineral density in AIDS patients on treatment with zidovudine/lamivudine plus abacavir or lopinavir/ritonavir

The aim of the study was to determine the factors that may contribute to decreases in bone mineral density (BMD) in patients with AIDS.

Initial Use of Echinocandins Does Not Negatively Influence Outcome in Candida parapsilosis Bloodstream Infection: A Propensity Score Analysis

BACKGROUND Concerns have arisen regarding the optimal antifungal regimen for Candida parapsilosis bloodstream infection (BSI) in view of its reduced susceptibility to echinocandins. METHODS The Prospective Population Study on Candidemia in Spain (CANDIPOP) is a prospective multicenter, population-based surveillance program on Candida BSI conducted through a 12-month period in 29 Spanish hospitals. Clinical isolates were identified by DNA sequencing, and antifungal susceptibility testing was performed by the European Committee on Antimicrobial Susceptibility Testing methodology. Predictors for clinical failure (all-cause mortality between days 3 to 30, or persistent candidemia for ≥72 hours after initiation of therapy) in episodes of C. parapsilosis species complex BSI were assessed by logistic regression analysis. We further analyzed the impact of echinocandin-based regimen as the initial antifungal therapy (within the first 72 hours) by using a propensity score approach. RESULTS Among 752 episodes of Candida BSI identified, 200 (26.6%) were due to C. parapsilosis species complex. We finally analyzed 194 episodes occurring in 190 patients. Clinical failure occurred in 58 of 177 (32.8%) of evaluable episodes. Orotracheal intubation (adjusted odds ratio [AOR], 2.81; P = .018) and septic shock (AOR, 2.91; P = .081) emerged as risk factors for clinical failure, whereas early central venous catheter removal was protective (AOR, 0.43; P = .040). Neither univariate nor multivariate analysis revealed that the initial use of an echinocandin-based regimen had any impact on the risk of clinical failure. Incorporation of the propensity score into the model did not change this finding. CONCLUSIONS The initial use of an echinocandin-based regimen does not seem to negatively influence outcome in C. parapsilosis BSI.

Dolutegravir efficacy at 48 weeks in key subgroups of treatment-naive HIV-infected individuals in three randomized trials

Objectives:Dolutegravir (DTG) has been studied in three trials in HIV treatment-naive participants, showing noninferiority compared with raltegravir (RAL), and superiority compared with efavirenz and ritonavir-boosted darunavir. We explored factors that predicted treatment success, the consistency of observed treatment differences across subgroups and the impact of NRTI backbone on treatment outcome. Design:Retrospective exploratory analyses of data from three large, randomized, international comparative trials: SPRING-2, SINGLE, and FLAMINGO. Methods:We examined the efficacy of DTG in HIV-infected participants with respect to relevant demographic and HIV-1-related baseline characteristics using the primary efficacy endpoint from the studies (FDA snapshot) and secondary endpoints that examine specific elements of treatment response. Regression models were used to analyze pooled data from all three studies. Results:Snapshot response was affected by age, hepatitis co-infection, HIV risk factor, baseline CD4+ cell count, and HIV-1 RNA and by third agent. Differences between DTG and other third agents were generally consistent across these subgroups. There was no evidence of a difference in snapshot response between abacavir/lamivudine (ABC/3TC) and tenofovir/emtricitabine (TDF/FTC) overall [ABC/3TC 86%, TDF/FTC 85%, difference 1.1%, confidence interval (CI) −1.8, 4.0 percentage points, P = 0.61] or at high viral loads (difference −2.5, 95% CI −8.9, 3.8 percentage points, P = 0.42). Conclusions:DTG is a once-daily, unboosted integrase inhibitor that is effective in combination with either ABC/3TC or TDF/FTC for first-line antiretroviral therapy in HIV-positive individuals with a variety of baseline characteristics.

Use of rituximab as a salvage therapy for HIV-associated multicentric Castleman disease.

Several approved therapies for multicentric Castleman disease (MCD) cannot be uniformly applied due to intolerable side effects. There is also a high percentage of recurrence of this disease despite treatment. Rituximab may be effective in controlling MCD in a subset of patients. This paper includes a brief case report and an extensive review of previously published cases. We observed an aggravation of concomitant cutaneous Kaposi sarcoma, and hypothesize that rituximab could have exacerbated it.

Bacteremic pneumococcal infections in immunocompromised patients without AIDS: the impact of β-lactam resistance on mortality

BACKGROUND Streptococcus pneumoniae is the leading cause of community-acquired pneumonia in the elderly, and in recent years it has arisen as an important pathogen in HIV-infected patients. However, there is a scarcity of information on clinical and therapeutic problems associated with pneumococcal infections in other immuno-compromised patients. The objective of this study was to assess the most relevant epidemiologic aspects, clinical features and prognostic factors of pneumococcal bacteremia in immunocompromised hosts without AIDS. METHODS This was a retrospective analysis of patients with pneumococcemia, carried out in a 600-bed, university-affiliated hospital in Madrid, Spain. Two-hundred and sixty patients were evaluated retrospectively; 69 (26.5%) immunocompromised patients based on strict case definitions were compared with a group composed of 191 non-immunocompromised hosts with a variety of chronic conditions. Conventional management of pneumococcal bacteremia according to clinical standards was assessed. The MICs of penicillin and other beta-lactam antibiotics, and related mortality and hospital mortality at 30 days, were measured. RESULTS A comparison of clinical manifestations of pneumococcemia between immunocompromised patients and non-immunocompromised patients did not show differences in the presence of fever, obtundation, type of lung involvement, frequency of primary bacteremia, or meningitis. Hospital-acquired pneumococcemia was significantly more frequent in immunocompromised patients (34.7% versus 6.8%, P<0.0001), and resistance to penicillin was also more common in pneumococcal strains isolated from these patients (37.5% versus 20%, P=0.0009). Septic shock occurred more frequently in immunocompromised patients, although the overall and related mortality were not significantly different from those found in non-immunocompromised patients (33.3% versus 22.5%, P=0.07, and 28.9% versus 20.9%, P=0.7 respectively). In the multivariate analysis, multilobar pneumonia (odds ratio (OR) 15.7; 95% CI 6.00-41.30; P<0.001), inadequate treatment (OR 12.20; 95% CI 4.10-37.20; P<0.001), obtundation (OR 5.80; 95% CI 2.20-15.00; P<0.001) and hospital-acquired bacteremia (OR 4.80; 95% CI 1.00-14.60; P<0.006) were associated with an increased risk of mortality in patients with pneumococcemia. Only multilobar pneumonia (OR 7.90; 95% CI 4.10-15.35; P<0.001) was significantly associated with an increased risk of mortality in immunocompromised patients. Patients with acute leukemia and lymphoma had a greater mortality rate than non-immunocompromised patients (53.8% related mortality, P=0.05). Analysis of these patients showed frequent inadequate empirical therapy with ceftazidime plus amikacin in the presence of beta-lactam resistance. CONCLUSIONS Much of the burden of pneumococcal bacteremia was attributable to immunosuppressive diseases. In immunocompromised patients, pneumococcemia was frequently acquired within the hospital during the treatment of the underlying condition, and resistance to penicillin was common. Patients with acute leukemia and lymphoma who develop fever and pneumonia should be treated with drugs active against beta-lactam-resistant pneumococci, irrespective of the setting in which the infection develops.

Long-Term Follow-Up of Asymptomatic HIV-Infected Patients Who Discontinued Antiretroviral Therapy

BACKGROUND Whether asymptomatic human immunodeficiency virus (HIV)-infected patients can interrupt treatment remains unknown. METHODS We performed a prospective, observational study of 46 patients who started therapy with >300 CD4+ cells/mm3 and/or <70,0000 HIV-1 RNA copies/mL. Patients had been receiving highly active antiretroviral therapy (HAART) for at least 6 months. HAART was discontinued, and plasma HIV-1 RNA loads and CD4+ cell counts were determined at 4-month intervals. RESULTS At the time of HAART discontinuation, the median CD4+ cell count was 793 cells/mm3, and all patients had undetectable viral loads. A rapid decrease of 173 cells/mm3 in the median CD4+ cell count was observed during the first 4 months after HAART was stopped, followed by a slower decrease of 234 cells/mm3 between months 5 and 20. The decrease in the median CD4+ cell count early after HAART discontinuation was inversely correlated with the increase that occurred during receipt of therapy (r=-0.653) and with the count at the time of HAART discontinuation (r=-0.589). The decrease in the median CD4+ cell count after the fourth month without HAART was correlated with the nadir count before HAART initiation (r=-0.349) and the increase during treatment (r=-0.322). The median follow-up duration was 20 months. After 12, 24, and 36 months of observation, 33 patients (71.7%), 22 patients (47.8%), and 16 patients (34.7%), respectively, remained free of therapy. Adverse clinical events were not seen, and all patients who reinitiated HAART responded rapidly. CONCLUSION Selected asymptomatic HIV-infected patients can safely discontinue therapy for prolonged periods of time.