Fernando M. Biscione

C-reactive protein-guided approach may shorten length of antimicrobial treatment of culture-proven late-onset sepsis: an intervention study.

Late-onset sepsis (LOS) (i.e., sepsis in a neonate after 72 hours of life) is associated with high mortality and significantly prolonged antibiotic exposure and hospital stay in neonates admitted to intensive care units (ICU). In this study, we assessed the reliability of serum C-reactive protein (CRP) as a determinant of antimicrobial treatment duration of LOS. From January 1996 to December 2002, all consecutive infants aged <28 days admitted to a single medical-surgical ICU and diagnosed with primary LOS were enrolled in a prospective, intervention trial with historical controls. Only blood culture-positive LOSs were included. Exclusion criteria were: age >28 days at diagnosis of LOS, development of site-specific infection, and central venous catheter-related LOS. From January 1996 to July 1998 (historical control group), antimicrobial treatment of LOS was offered for at least 14 days. From August 1998 to December 2002 (intervention group), neonates underwent serial semiquantitative measurements of serum CRP, and antimicrobial treatment was discontinued when CRP was <12 mg/L. Primary efficacy endpoint was the duration of antimicrobial therapy. Secondary efficacy endpoints were the proportion of relapsing sepsis within 72 hours of antibiotic withdrawal and the overall mortality rate. The historical control group comprised 76 neonates developing 85 episodes of LOS; 138 LOS occurring in 120 patients comprised the intervention group. Length of antimicrobial treatment of LOS was significantly shorter during the second study period (16 days vs. 9 days, p<0.001). Secondary efficacy endpoints showed similar rates of relapsing sepsis and overall mortality in both time periods.

Comparison of the Risk of Surgical Site Infection After Laparoscopic Cholecystectomy and Open Cholecystectomy

We assessed the independent contributions of the surgical approach and other variables of the National Nosocomial Infections Surveillance System (NNIS) surgical patient component to the surgical site infection risk after cholecystectomy. Laparoscopic cholecystectomy was associated with a lower overall risk of surgical site infection and a lower risk of incisional infection but not a reduced risk of organ-space infection, compared with open cholecystectomy. The contribution of most of the variables of the NNIS surgical patient component to the risk of surgical site infection depended on the depth of the infection.

Slow clinical improvement after treatment initiation in Leishmania/HIV coinfected patients

INTRODUCTION In Brazil there is a large area of overlap of visceral leishmaniasis (VL) and HIV infection, which favored a increased incidence of coinfection Leishmania/HIV. METHODS This study evaluated 65 consecutive patients with VL and their clinical response to treatment in two health care settings in Belo Horizonte, Brazil. RESULTS At baseline, the clinical picture was similar between both groups, although diarrhea and peripheral lymphadenomegaly were more frequent in HIV-infected subjects. HIV-positive patients had lower median blood lymphocyte counts (686/mm³ versus 948/mm³p = 0.004) and lower values of alanine aminotransferase (ALT) (48IU/L versus 75.6IU/L p = 0.016) than HIV-negative patients. HIV-positive status (hazard ratio = 0.423, p = 0.023) and anemia (HR = 0.205, p = 0.002) were independent negative predictors of complete clinical response following antileishmanial treatment initiation. CONCLUSIONS This study reinforces that all patients with VL should be tested for HIV infection, regardless of their clinical picture. This practice would allow early recognition of coinfection with initiation of antiretroviral therapy and, possibly, reduction in treatment failure.

Virologic and immunologic effectiveness at 48 weeks of darunavir-ritonavir-based regimens in treatment-experienced persons living with HIV-1 infection in clinical practice: a multicenter Brazilian cohort.

Introduction: Published data addressing the effectiveness of darunavir–ritonavir (DRV/r)-based therapy for multiexperienced patients in developing countries are scarce. This study evaluated the 48-week virologic and immunologic effectiveness of salvage therapy based on DRV/r for the treatment of multidrug-experienced HIV-1-infected adults in Brazil. Materials and Methods: A multicenter retrospective cohort study was carried out with multidrug-experienced adults who were on a failing antiretroviral therapy and started a DRV/r-based salvage therapy between 2008 and 2010. The primary effectiveness end point was the proportion of patients with virologic success (plasma HIV-1 RNA <50 copies/mL at week 48). Results: At 48 weeks, 73% of the patients had HIV-RNA <50 copies/mL and a mean increase of 108 CD4 cells/mm3. Higher baseline viral load, lower baseline CD4 count, younger age, and 3 or more DRV/r-associated resistance mutations were significantly predictive of virologic failure. Concomitant use of raltegravir was strongly associated with virologic success. Conclusion: The use of DRV/r-based regimens for salvage therapy is an effective strategy in the clinical care setting of a developing country.

Accounting for incomplete postdischarge follow-up during surveillance of surgical site infection by use of the National Nosocomial Infections Surveillance system's risk index.

OBJECTIVE We examined the usefulness of a simple method to account for incomplete postdischarge follow-up during surveillance of surgical site infection (SSI) by use of the National Nosocomial Infections Surveillance (NNIS) systems risk index. DESIGN Retrospective cohort study that used data prospectively collected from 1993 through 2006. SETTING Five private, nonuniversity healthcare facilities in Belo Horizonte, Brazil. PATIENTS Consecutive patients undergoing the following NNIS operative procedures: 20,981 operations on the genitourinary system, 11,930 abdominal hysterectomies, 7,696 herniorraphies, 6,002 cholecystectomies, and 6,892 laparotomies. METHODS For each operative procedure category, 2 SSI risk models were specified. First, a model based on the NNIS systems risk index variables was specified (hereafter referred to as the NNIS-based model). Second, a modified model (hereafter referred to as the modified NNIS-based model), which was also based on the NNIS systems risk index, was specified with a postdischarge surveillance indicator, which was assigned the value of 1 if the patient could be reached during follow-up and a value of 0 if the patient could not be reached. A formal comparison of the capabilities of the 2 models to assess the risk of SSI was conducted using measures of calibration (by use of the Pearson goodness-of-fit test) and discrimination (by use of receiver operating characteristic curves). Goodman-Kruskal correlations (G) were also calculated. RESULTS The rate of incomplete postdischarge follow-up varied between 29.8% for abdominal hysterectomies and 50.5% for cholecystectomies. The modified NNIS-based model for laparotomy did not show any significant benefit over the NNIS-based model in any measure. For all other operative procedures, the modified NNIS-based model showed a significantly improved discriminatory ability and higher G statistics, compared with the NNIS-based model, with no significant impairment in calibration, except if used to assess the risk of SSI after operations on the genitourinary system or after a cholecystectomy. CONCLUSIONS Compared with the NNIS-based model, the modified NNIS-based model added potentially useful clinical information regarding most of the operative procedures. Further work is warranted to evaluate this method for accounting for incomplete postdischarge follow-up during surveillance of SSI.

Virologic and immunologic effectiveness of darunavir-based salvage therapy in HIV-1-infected adults in a Brazilian clinical practice setting: results of a multicenter and retrospective cohort study.

BACKGROUND Darunavir has been proven efficacious for antiretroviral-experienced HIV-1-infected patients in randomized trials. However, effectiveness of darunavir-based salvage therapy is understudied in routine care in Brazil. METHODS Retrospective cohort study of HIV-1-infected patients from three public referral centers in Belo Horizonte, who received a darunavir-based therapy between 2008 and 2010, after virologic failure. Primary endpoint was the proportion of patients with viral load<50 copies/mL at week 48. Change in CD4 cell count was also evaluated. Outcome measures were analyzed on an intent-to-treat basis applied to observational studies. Sensitivity analysis was conducted to evaluate the impact of missing data at week 48. Predictors of virologic failure were examined using rare-event, finite sample, bias-corrected logistic regression. RESULTS Among 108 patients, the median age was 44.2 years, and 72.2% were male. They had long-standing HIV-1 infection (median 11.6 years) and advanced disease (76.9% had an AIDS-defining event). All patients had previously received protease inhibitors and nucleoside reverse transcriptase inhibitors, 75% nonnucleoside reverse transcriptase inhibitors, and 4.6% enfuvirtide. The median length of protease inhibitor use was 8.9 years, and 90.8% of patients had prior exposure to unboosted protease inhibitor. Genotypic resistance profile showed a median of three primary protease inhibitor mutations and 10.2% had three or more darunavir resistance-associated mutations. Virologic success at week 48 was achieved by 78.7% (95% CI=69.7-86%) of patients and mean CD4 cell count increase from baseline was 131.5 cells/μL (95% CI=103.4-159.6). In multiple logistic regression analysis, higher baseline viral load (RR=1.04 per 10,000 copies/mL increase; 95% CI=1.01-1.09) and higher number of darunavir resistance-associated mutations (RR=1.23 per each; 95% CI=0.95-1.48) were independently associated with virologic failure. CONCLUSION Virologic suppression is a realistic endpoint for most treatment-experienced patients who begin a darunavir-based therapy outside the controlled conditions of a randomized trial, at routine care settings.

Performance, Revision, and Extension of the National Nosocomial Infections Surveillance System’s Risk Index in Brazilian Hospitals

OBJECTIVE To assess the benefit of using procedure-specific alternative cutoff points for National Nosocomial Infections Surveillance (NNIS) risk index variables and of extending surgical site infection (SSI) risk prediction models with a postdischarge surveillance indicator. DESIGN Open, retrospective, validation cohort study. SETTING Five private, nonuniversity Brazilian hospitals. PATIENTS Consecutive inpatients operated on between January 1993 and May 2006 (other operations of the genitourinary system [n = 20,723], integumentary system [n = 12,408], or musculoskeletal system [n = 15,714] and abdominal hysterectomy [n = 11,847]). METHODS For each procedure category, development and validation samples were defined nonrandomly. In the development samples, alternative SSI prognostic scores were constructed using logistic regression: (i) alternative NNIS scores used NNIS risk index covariates and cutoff points but locally derived SSI risk strata and rates, (ii) revised scores used procedure-specific alternative cutoff points, and (iii) extended scores expanded revised scores with a postdischarge surveillance indicator. Performances were compared in the validation samples using calibration, discrimination, and overall performance measures. RESULTS The NNIS risk index showed low discrimination, inadequate calibration, and predictions with high variability. The most consistent advantage of alternative NNIS scores was regarding calibration (prevalence and dispersion components). Revised scores performed slightly better than the NNIS risk index for most procedures and measures, mainly in calibration. Extended scores clearly performed better than the NNIS risk index, irrespective of the measure or operative procedure. CONCLUSIONS Locally derived SSI risk strata and rates improved the NNIS risk indexs calibration. Alternative cutoff points further improved the specification of the intrinsic SSI risk component. Controlling for incomplete postdischarge SSI surveillance provided consistently more accurate SSI risk adjustment.

Short communication: Effectiveness at 48 weeks of switching from enfuvirtide to raltegravir in virologically suppressed multidrug-resistant HIV type 1-infected patients in a Brazilian cohort.

Abstract The effectiveness of switching from enfuvirtide to raltegravir in HIV-1-infected patients on a suppressive antiretroviral regimen has been poorly studied in the clinical practice of developing countries. We conducted a multicenter retrospective cohort study in HIV-1-infected, multidrug-experienced adults (≥18 years old) with plasma HIV-1-RNA <400 copies/ml for at least 4 months on an enfuvirtide-containing therapy between 2005 and 2010, in whom the attending physician switched from enfuvirtide to raltegravir. Effectiveness endpoints were measured at week 48 after switch. Analyses were conducted on an intent-to-treat basis and two strategies for handling missing outcome data were used (hereafter, strategies 1 and 2). Overall, 87 patients were eligible for analysis. At baseline, the median CD4+ T cell count was 400 cells/μl and 91.9% of patients had <50 HIV-1-RNA copies/ml. At week 48, the proportions of patients with plasma HIV-1-RNA <50 and <400 copies/ml were, respectively, 86.2% (95% CI=77.1; 9...The effectiveness of switching from enfuvirtide to raltegravir in HIV-1-infected patients on a suppressive antiretroviral regimen has been poorly studied in the clinical practice of developing countries. We conducted a multicenter retrospective cohort study in HIV-1-infected, multidrug-experienced adults (≥18 years old) with plasma HIV-1-RNA <400 copies/ml for at least 4 months on an enfuvirtide-containing therapy between 2005 and 2010, in whom the attending physician switched from enfuvirtide to raltegravir. Effectiveness endpoints were measured at week 48 after switch. Analyses were conducted on an intent-to-treat basis and two strategies for handling missing outcome data were used (hereafter, strategies 1 and 2). Overall, 87 patients were eligible for analysis. At baseline, the median CD4(+) T cell count was 400 cells/μl and 91.9% of patients had <50 HIV-1-RNA copies/ml. At week 48, the proportions of patients with plasma HIV-1-RNA <50 and <400 copies/ml were, respectively, 86.2% (95% CI=77.1; 92.7%) and 88.5% (95% CI=79.9; 94.3%) (strategies 1 and 2) and 89.7% (95% CI=81.3; 95.2%) and 90.8% (95% CI=82.7; 95.9%) (strategies 1 and 2). This was a -10.3% (95% CI=-2.8; -17.9%) and -9.2% (95% CI=-2; -16.4%) difference from baseline in the proportion of patients with plasma HIV-1-RNA <400 copies/ml. The median increase in CD4(+) T cell counts was 41 and 64 cells/μl (p<0.001) (strategies 1 and 2). No patient withdrew raltegravir or developed opportunistic infections, but one was diagnosed with HIV-related dementia. In conclusion, switching from enfuvirtide to raltegravir in patients on a virologically suppressive regimen is an effective strategy even in a Brazilian clinical setting.