Outcome of hospitalized MDR-TB patients: Israel 2000–2005

MDR-TB has emerged in Israel following an immigrations wave from the Former Soviet Union (FSU) and Ethiopia. The purpose of this study was to outline characteristics and outcome of hospitalized MDR-TB patients. We retrospectively summarized charts of MDR-TB patients hospitalized in the national referral tuberculosis centers from January 2000 to December 2005, and followed them for 2 years. One hundred thirty-two patients were identified with a median age of 40 years and male predominance (77%). The majority of the patients were immigrants from FSU (83%) and Ethiopia (7.6%). They were characterized by alcohol (25.8%) and IV drug abuse (23.5%), presented with advanced disease manifested by hypoalbuminemia (50.8%) and smear positivity (70.5%). Cure was achieved in 50.3% and 30.4% died. Factors independently associated with death were patients’ age (OR = 1.036 for each year, 95%CI 1.0–1.1, p = 0.014), hypoalbuminemia (OR = 2.95, 95%CI 1.1–7.6, p = 0.025), smear positivity at diagnosis (OR = 3.7, 95%CI 1.2–11.4, p = 0.023), alcohol abuse (OR = 4.8, 95%CI 1.7–13.7, p = 0.004) and XDR-TB resistance pattern (OR 8.3, 95%CI 1.5–44.6, p = 0.014). This study brings out the poor prognosis of a highly vulnerable immigration population. Efforts should be focused on earlier diagnosis and treatment in a well controlled hospital environment and to professional support groups to attend to this population’s special needs.     

Comparison of isoniazid monoresistant tuberculosis with drug-susceptible tuberculosis and multidrug-resistant tuberculosis

Limited data exist about the clinical characteristics of Mycobacterium tuberculosis (TB) isolates with resistance to isoniazid (IZN). We describe the demographic and clinical characteristics and risk factor information for persons with IZN monoresistant (resistant to isoniazid) TB compared with drug-susceptible TB and multidrug-resistant (MDR) TB. From 2002 to 2009, 590 cases of TB were diagnosed. Of these, 44 (7.5%) developed MDR-TB and 38 (6.4%) had IZN monoresistant TB. Among the IZN monoresistant TB patients, more common demographic characteristics were former resident of the Soviet Union immigrant, smoker, and previous history of TB (p = 0.005, 0.025, and 0.005, respectively), while HIV, weight loss, and hemoptysis were less common (p = 0.005 for all parameters). The mean length of treatment was 24 ± 4 months for MDR-TB, 10 ± 3 months for IZN monoresistant TB cases, and 8 ± 2 months for all other TB cases. The directly observed therapy (DOT) rate was similar in all three groups. However, treatment failure, completion of TB treatment, and mortality were all similar in drug-susceptible TB and higher in MDR-TB. In multivariate analysis, only a history of previous TB (odds ratio [OR] 1.4; 95% confidence interval [CI]: 1.2–1.6) was significantly associated with IZN monoresistant TB. IZN monoresistant TB has distinct characteristics. However, the length of treatment and outcome are similar to drug-susceptible TB cases.     

Determinants for the Development of Oropharyngeal Colonization or Infection by Fluconazole-Resistant Candida Strains in HIV-Infected Patients

 A point prevalence study to document oral yeast carriage was undertaken. Risk factors for the development of oropharyngeal colonization or infection by fluconazole-resistant Candida strains in HIV-infected patients were investigated with a case-control design. Cases included all patients with fluconazole-resistant strains (MIC≥64 μg/ml), and controls were those with susceptible (MIC≤8 μg/ml) or susceptible-dependent-upon-dose (MIC 16–32 μg/ml) strains. One hundred sixty-eight Candida strains were isolated from 153 (88%) patients, 28 (16%) of whom had oropharyngeal candidiasis. Overall, 19 (12%) of the patients harbored at least one resistant organism (MIC≥64 μg/ml). Among patients with resistant strains, tuberculosis (P<0.001), esophageal candidiasis (P=0.001), clinical thrush (P<0.001), and a CD4+ cell count <200/mm³ (P=0.03) were more frequent. These patients had also been treated more commonly with antituberculous drugs (adjusted odds ratio [OR] 6.13; 95% confidence interval [CI] 2.11–17.80), ciprofloxacin (OR 6.0; 95% CI 1.23–29.26), fluconazole (OR 4.59; 95% CI 1.55–13.52), and steroids (OR 4.13; 95% CI 1.11–15.39). Multivariate analysis showed that the determinants for fluconazole resistance were therapy with antituberculous drugs (OR 3.61; 95% CI 1.08–12.07;P=0.03) and one of the following: previous tuberculosis (OR 3.53; 95% CI 1.08–14.57;P=0.03) or fluconazole exposure (OR 3.41; 95% CI 1.10–10.54). Findings from this study indicate that treatment with antituberculous drugs, previous tuberculosis, and fluconazole exposure are the strongest determinants for development of oropharyngeal colonization or infection by fluconazole-resistant Candida strains in HIV-infected patients.     

5′ Regulatory and 3′ Untranslated Region Polymorphisms of Vitamin D Receptor Gene in South Indian HIV and HIV–TB Patients

Introduction  Vitamin D receptor (VDR) gene polymorphisms in the 5′ regulatory region (Cdx2 and A-1012G), coding region (FokI), and 3′ untranslated region (UTR; BsmI, ApaI, and TaqI) were studied to find out whether these polymorphisms are associated with susceptibility to or protection against HIV-1 and development of tuberculosis (TB) in human immunodeficiency virus (HIV)-1-infected patients. Study Subjects and Methods  The study was carried out in 131 HIV patients without TB (HIV+ TB−) and 113 HIV patients with TB (HIV+ TB+; includes 82 patients with pulmonary TB (HIV+ PTB+) and 31 with extra pulmonary TB), 108 HIV-negative pulmonary TB patients (HIV− PTB+), and 146 healthy controls. Results  Among the 5′ regulatory and coding region polymorphisms, significantly increased frequency of G/A genotype of Cdx-2 was observed in HIV+ TB− group compared to controls (p = 0.012, odds ratio (OR) 1.89 95% confidence interval (CI) 1.14–3.15). In the 3′ UTR genotypes, a decreased frequency of b/b genotype of BsmI in total HIV patients (p = 0.014, OR 0.54 95% CI 0.32–0.89) and increased frequencies of A/A genotype of ApaI in HIV+ TB+ patients (p = 0.041, OR 1.77 95% CI 1.02–3.06) and t/t genotype of TaqI in HIV+ PTB+ patients (p = 0.05, OR 2.32 95% CI 0.99–5.46) were observed compared to controls. Haplotype analysis revealed significantly increased frequencies of 3′ UTR haplotype B-A-t in HIV+ TB+ and HIV+ PTB+ groups (Pc = 0.030, OR 1.75 95% CI 1.14–2.66) and decreased frequencies of b-A-T haplotype in total HIV patients (Pc = 0.012, OR 0.46 95% CI 0.27–0.77), HIV+ TB− (p = 0.031 OR 0.48 95% CI 0.25–0.89), and HIV+ PTB+ groups (Pc = 0.04, OR 0.47 95% CI 0.23–0.89) compared to controls. Conclusions  The results suggest that VDR gene 3′ UTR haplotype b-A-T may be associated with protection against HIV infection while B-A-t haplotype might be associated with susceptibility to development of TB in HIV-1-infected patients.     

Clinical and microbiological characteristics of urine culture-confirmed genitourinary tuberculosis at medical centers in Taiwan from 1995 to 2007

All patients with urine culture-confirmed genitourinary tuberculosis (GUTB) diagnosed between 1995 and 2007 at two medical centers in northern Taiwan were included in this retrospective study. Genotypes of 48 preserved Mycobacterium tuberculosis (MTB) isolates from these patients were determined by spoligotyping and double repetitive element PCR (DRE-PCR) analysis. Among the 64 patients, 38 (59.4%) were male with a mean ±SD age of 60.3 ± 16.1 years old. The overall mortality rate was 26.2%. Poor prognostic factors included age over 65 years (HR = 4.03; 95%; CI: 1.27–12.76), cardiovascular disease (HR = 5.96; 95% CI: 1.98–17.92), receiving steroids (HR = 10.16; 95% CI: 2.27–45.47), not being treated (HR 4.81; 95% CI 1.12–20.67). Spoligotyping and DRE-PCR of the 48 MTB isolates revealed that 20 (41.7%) belonged to the Beijing family and 40 (83.3%) had a clustering pattern. Identification of a Beijing family isolate was not correlated with drug resistance or mortality. Clustering strains were likely to be resistant to isoniazid (OR = 4.71; 95% CI: 1.10 to 23.53). In this study of patients with urine culture-confirmed GUTB, age and coexisting diseases were independently associated with an unfavorable outcome. The Beijing family was the dominant genotype of GUTB isolates, but did not correlate with drug resistance or outcome.     

Multi-drug-resistant gram-negative bacterial infection in surgical patients hospitalized in the ICU: a cohort study

We sought to identify risk factors for postoperative infections, caused by multi-drug-resistant gram-negative bacteria (MDR-GNB) in surgical patients. This was a retrospective cohort study among patients hospitalized in the intensive care unit (ICU) for more than 5 days, following general surgical operations. Comparison of patients who developed infection caused by MDR-GNB with the remainder of the cohort showed that every minute of operative time, use of special treatments during hospitalization (antineoplastic, immunosuppressive or immunomodulating therapies), every day of metronidazole, and every day of carbapenems use, increased patients’ odds to acquire an infection caused by MDR-GNB by 0.7%, 8.9 times, 9%, and 9%, respectively [OR (95% CI): 1.007 (1.003–1.011), p = 0.001; 8.9 (1.8–17.3), p = 0.004; 1.09 (1.04–1.18), p = 0.039; 1.09 (1.01–1.18), p = 0.023, respectively]. The above were adjusted in the multivariable analysis for the confounder of time distribution of infections caused by MDR-GNB. Finally, the secondary comparison, with patients that did not develop any infection, showed that patients who had received antibiotics, within 3 months prior to admission, had 3.8 times higher odds to acquire an infection caused by MDR-GNB [OR (95% CI): 3.8 (1.07–13.2), p = 0.002]. This study depicts certain, potentially modifiable, risk factors for postoperative infections in patients hospitalized in the ICU for more than 5 days.     

Infectious endocarditis in patients with cirrhosis of the liver: a model of infection in the frail patient

The purposes of this paper was to discover whether cirrhosis is a predisposing cause of infectious endocarditis (IE) and to determine the microbiology, prognosis and the role of cardiac surgery on mortality. A review of cases of IE at a university-affiliated hospital over a period of 10 years was conducted. Thirty-one (9.8%) patients among 316 cases of IE had hepatic cirrhosis. Valve disorders were present in 62.2% of cirrhotic patients and infection occurred on the aortic (48%) and mitral valves (45%). Endocarditis was hospital-acquired in 14 (45%) and 11 (17.7%) cirrhotic patients and controls, respectively (odds ratio [OR] 3.82; 95% confidence interval [CI]: 1.46–9.99; p = 0.005). Staphylococcus aureus was the most common causative microorganism, but β-hemolytic streptococci were most frequently isolated in cirrhotic patients (OR 8.75; 95% CI: 1.7–45.2; p = 0.001). Renal failure was more frequent in patients with cirrhosis (OR 8.23; 95% CI: 3.06–22.2; p = 0.001). Cirrhotic patients had a higher mortality (51% vs. 17.7%; OR 4.95; 95% CI: 1.89–12.91; p = 0.001) associated with the severity of liver disease. Valve replacement was performed less frequently in cirrhotic patients (56.2% vs. 92%) and the operative mortality was extremely high in patients at stages B and C. Hepatic cirrhosis is a frequent comorbid condition in patients with endocarditis. Due to the presence of severe hepatic dysfunction, cardiac surgery is not undertaken even when indicated and mortality is high in stages B and C. Endocarditis is a serious hazard for hospitalized cirrhotic patients.     

LYVE-1 upregulation and lymphatic invasion correlate with adverse prognostic factors and lymph node metastasis in neuroblastoma

Neuroblastoma (NB) accounts for 15% of all childhood cancer deaths. The majority of patients have widespread lymphatic and/or haematogenous metastases at diagnosis, but lymphangiogenesis has not been well documented. Sixty-seven NBs were immunostained for the lymphatic endothelial marker, LYVE-1, and the lymphatic density (LD) and lymphatic invasion (LI), were counted in LYVE-1-expressing lymphatics. LYVE-1-stained lymphatic vessels and LI were present in 26/67 (39%) and 14/67 (21%) of the NBs, respectively. Central LD (CLD) and LI were higher in NBs from stage 4 (p = 0.012, p = 0.004, respectively), high-risk group (p = 0.030, p = 0.002), NBs with high mitosis karyorrhexis index (MKI) (p = 0.011, p = 0.005), unfavourable histology group (p = 0.040, p = 0.017) and distant lymph node metastasis (LNM) (p < 0.001 for each). Marginal LD (MLD) was higher in patients with LNM (p < 0.001). CLD and MLD correlated with LI (p < 0.001 each). Total LYVE-1 protein levels, quantified by a sensitive enzyme-linked immunosorbent assay (n = 55), were also higher in NBs from patients with stage 4 disease (p = 0.046), high-risk group (p = 0.028), MYCN-amplified NBs (p = 0.034) and LNM (p = 0.038). Kaplan–Meier analysis showed that the presence of CLD was associated with both worse OS at 5 years (77% [95% CI: 62–87%] versus 60% [95% CI: 32–80%], p = 0.062) and EFS (74% [95% CI: 58–85%] versus 43% [95% CI: 15–69%], p = 0.070) and LI with OS (71% [95% CI: 57–81%] versus 56% [95% CI: 26–78%], p = 0.055). Significant upregulation of LYVE-1 and the presence of LI in patients with stage 4 and high-risk disease, MYCN-amplification and LNM suggests that LYVE-1 may have value as predictors of outcome.     

Impact of multi-drug-resistant <Emphasis Type="Italic">Acinetobacter baumannii</Emphasis> on clinical outcomes

We conducted a retrospective matched cohort study to examine the impact of isolation of multi-drug-resistant (MDR) Acinetobacter baumannii on patient outcomes. Cases from whom MDR A. baumannii was isolated in a clinical culture (n = 118) were compared with controls from whom MDR A. baumannii was not isolated (n = 118). Cases and controls were matched according to ward, calendar month of hospitalization, and duration of hospitalization before culture. The following outcomes were compared in multivariable analysis: in-hospital mortality, length of stay, need for mechanical ventilation, and functional status at discharge. MDR A. baumannii was determined to be a pathogen in 72% of cases. In 36% of cases, the patient died, versus 21% of controls (odds ratio [OR] 2.21, 95% confidence interval [CI] 1.17–4.16, P = 0.014). Median length of stay for surviving cases was 17 days, versus 11 for surviving controls (multiplicative effect 1.55, 95% CI 0.99–2.44, P = 0.057). Fifty-two percent of cases required mechanical ventilation, versus 25% of controls (OR 3.72, 95% CI 1.91–7.25, P<0.001); 60% of surviving cases were discharged with reduced functional status, versus 38% of controls (OR 4.4, 95% CI 1.66–11.61, P = 0.003). In multivariable analysis, clinical isolation of MDR A. baumannii remained a significant predictor of mortality (OR 6.23, 95% CI 1.31–29.5, P = 0.021), need for mechanical ventilation (OR 7.34, 95% CI 2.24–24.0, P<0.001), and reduced functional status on discharge (OR 7.93, 95% CI 1.1–56.85, P = 0.039). Thus, MDR A. baumannii acquisition is associated with severe adverse outcomes, including increased mortality, need for mechanical ventilation, and reduced functional status.     

Effects of acute <Emphasis Type="Italic">Plasmodium falciparum</Emphasis> malaria on body weight in children in an endemic area

The impacts of acute falciparum malaria on body weight and the host and parasite factors predictive of change in body weight were characterized in 465 prospectively studied children in an endemic area of southwest Nigeria. Pre-treatment weights were significantly lower than the 14 to 28-day post-treatment weights (P = 0.0001). In 187 children, fractional fall in body weight (FFBW) exceeded 4.9%. FFBW correlated negatively with age and body weight (P = 0.014 and 0.0001, respectively), but not with enrolment parasitaemia. In a multiple regression model, an age ≤5 years (AOR = 2.03, 95% CI 1.2–3.2, P = 0.003), a hematocrit ≤29% (AOR = 1.6, 95% CI 1.0–2.3, P = 0.037), and a body weight ≤9.6 kg (AOR = 5.4, 95% CI 1.7–20, P = 0.003) were independent predictors of FFBW ≥5% at presentation. Children who, after initial clearance, had recurrence of their parasitaemia within 28 days had a significantly higher propensity not to gain weight than children who were aparasitaemic after treatment (log-rank statistic 6.76, df = 1, P = 0.009). These results indicate that acute malaria contribute to sub-optimal growth in young children and may have implications for malaria control efforts in sub-Saharan Africa.     

Warfarin therapy and incidence of cerebrovascular complications in left-sided native valve endocarditis

Anticoagulant therapy has been anticipated to increase the risk of cerebrovascular complications (CVC) in native valve endocarditis (NVE). This study investigates the relationship between ongoing oral anticoagulant therapy and the incidence of symptomatic CVC in left-sided NVE. In a prospective cohort study, the CVC incidence was compared between NVE patients with and without ongoing warfarin. Among 587 NVE episodes, 48 (8%) occurred in patients on warfarin. A symptomatic CVC was seen in 144 (25%) patients, with only three on warfarin. CVC were significantly less frequent in patients on warfarin (6% vs. 26%, odds ratio [OR] 0.20, 95% confidence interval [CI] 0.06–0.6, p = 0.006). No increase in haemorrhagic lesions was detected in patients on warfarin. Staphylococcus aureus aetiology (adjusted OR [aOR] 6.3, 95% CI 3.8–10.4) and vegetation length (aOR 1.04, 96% CI 1.01–1.07) were risk factors for CVC, while warfarin on admission (aOR 0.26, 95% CI 0.07–0.94), history of congestive heart failure (adjusted OR 0.22, 95% CI 0.1–0.52) and previous endocarditis (aOR 0.1, 95% CI 0.01–0.79) correlated with lower CVC frequency.     

The epidemiology of extraintestinal non-typhoid Salmonella in Israel: the effects of patients’ age and sex

Extraintestinal disease occurs in 5–8% of non-typhoid Salmonella enterica (NTS) infections and is more likely to be associated with hospitalization and death. The study examined the epidemiology of extraintestinal NTS infections in Israel and the possible effects of patients’ age and sex. NTS isolates passively submitted to the National Salmonella Reference Center during 1996–2006 were the source for the study cohort. Poisson regression models were used to assess incidence trends over the study years and to evaluate the effects of patients’ age and sex on the incidence of extraintestinal NTS manifestations. A total of 36,822 stool and 1,415 (3.7%) patient-unique NTS isolates from blood (74.1%), urine (18.3%), and other sources (3.7%) were studied. Serotypes Enteritidis, Virchow, and Typhimurium accounted for 66.3% of the isolates. Analysis showed a highly significant quadratic (U-shaped) relationship between patients’ age and the incidence of extraintestinal isolation (p < 0.001), with increasing risk in the two extremes of age. Differences between the incidence of blood and urine sources were significant in patients <10 and ≥60 years old (relative risk [RR] = 5.88, 95% confidence interval [CI] 3.36–10.30, p < 0.001 and RR = 1.66, 95% CI 1.09–2.53, p = 0.017, respectively). Males ≥60 years of age were more likely than females of the same age to have bacteremia (RR = 1.90, 95% CI 1.39–2.61, p > 0.001) and less likely to have urinary NTS isolation (RR = 0.50, 95% CI 0.28–0.89, p = 0.018). Serotype Virchow had the highest incidence in patients <10 years of age, while serotype Enteritidis had the highest incidence in patients ≥60 years old. The study revealed a complex effect of patients’ age and sex on the epidemiology of extraintestinal NTS manifestations.     

Elevated soluble urokinase plasminogen activator receptor (suPAR) predicts mortality in Staphylococcus aureus bacteremia

The soluble form of urokinase-type plasminogen activator receptor (suPAR) is a new inflammatory marker. High suPAR levels have been shown to associate with mortality in cancer and in chronic infections like HIV and tuberculosis, but reports on the role of suPAR in acute bacteremic infections are scarce. To elucidate the role of suPAR in a common bacteremic infection, the serum suPAR levels in 59 patients with Staphylococcus aureus bacteremia (SAB) were measured using the suPARnostic™ ELISA assay and associations to 1-month mortality and with deep infection focus were analyzed. On day three, after the first positive blood culture for S. aureus, suPAR levels were higher in 19 fatalities (median 12.3; range 5.7–64.6 ng/mL) than in 40 survivors (median 8.4; range 3.7–17.6 ng/mL, p = 0.002). This difference persisted for 10 days. The presence of deep infection focus was not associated with elevated suPAR levels as compared to patients with no deep infection focus. suPAR was found to be prognostic for mortality in receiver operator characteristic (ROC) curve analysis, which was not observed for serum C-reactive protein (CRP); the area under the curve (AUC) for suPAR was 0.754 (95% confidence interval [CI], 0.615–0.894, p = 0.003) and for CRP, it was 0.596 (95% CI, 0.442–0.750, p = 0.253). The optimal suPAR cut-off value in predicting 1-month mortality was 9.25 ng/mL. In conclusion, our study demonstrates that the new promising biomarker, serum suPAR concentration, was able to predict mortality in SAB.     

Pseudomonas aeruginosa Bacteremia in Patients Infected with Human Immunodeficiency Virus Type 1

 A prospective analysis of 43 episodes of Pseudomonas aeruginosa bacteremia in HIV-1-infected subjects was performed and the results compared with the incidence and outcome of Pseudomonas aeruginosa bacteremia in other high-risk patients, such as transplant recipients, leukemia patients, or patients hospitalized in the intensive care unit. The incidence of bacteremia/fungemia as a whole and of gram-negative and Pseudomonas aeruginosa bacteremia in particular was greater in HIV-1-infected subjects than in the unselected general population admitted. In contrast, the incidence of Pseudomonas aeruginosa bacteremia in HIV-1-infected patients did not differ from that in patients with other high-risk conditions. In patients with HIV-1 infection, independent risk factors for presenting Pseudomonas aeruginosa bacteremia were nosocomial origin (OR, 2.7; 95% CI, 1.3–5.7), neutropenia (OR, 2.7; 95% CI, 1.07–6.8), previous treatment with cephalosporins (OR, 3.6; 95% CI, 1.1–11.6), and a CD4+ cell count lower than 50 cells/mm³ (OR, 3.1; 95% CI, 1.7–8.6). Primary bacteremia and pneumonia were the most common forms of presentation. Fourteen (33%) patients died as a consequence of the bacteremia. The presence of severe sepsis (OR, 17.5; 95% CI, 3.2–68) and the institution of inappropriate definitive antibiotic therapy (OR, 2.7; 95% CI, 1.1–13) were independently associated with a poor outcome. One year after the development of bacteremia, only eight (19%) patients remained alive.     

Fungal colonization and/or infection in non-neutropenic critically ill patients: results of the EPCAN observational study

The purpose of this paper is to determine the incidence of fungal colonization and infection in non-neutropenic critically ill patients and to identify factors favoring infection by Candida spp. A total of 1,655 consecutive patients (>18 years of age) admitted for ≥7 days to 73 medical-surgical Spanish intensive care units (ICUs) participated in an observational prospective cohort study. Surveillance samples were obtained once a week. One or more fungi were isolated in different samples in 59.2% of patients, 94.2% of which were Candida spp. There were 864 (52.2%) patients with Candida spp. colonization and 92 (5.5%) with proven Candida infection. In the logistic regression analysis risk factors independently associated with Candida spp. infection were sepsis (odds ratio [OR] = 8.29, 95% confidence interval [CI] 5.07–13.6), multifocal colonization (OR = 3.49, 95% CI 1.74–7.00), surgery (OR = 2.04, 95% CI 1.27–3.30), and the use of total parenteral nutrition (OR = 4.37, 95% CI 2.16–8.33). Patients with Candida spp. infection showed significantly higher in-hospital and intra-ICU mortality rates than those colonized or non-colonized non-infected (P < 0.001). Fungal colonization, mainly due to Candida spp., was documented in nearly 60% of non-neutropenic critically ill patients admitted to the ICU for more than 7 days. Proven candidal infection was diagnosed in 5.5% of cases. Risk factors independently associated with Candida spp. infection were sepsis, multifocal colonization, surgery, and the use of total parenteral nutrition.     

Predictors of mortality in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia: the role of empiric antibiotic therapy

The objective of this study was to evaluate prognostic factors and the influence of different empiric antibiotic therapies on outcome and mortality in a cohort of 100 inpatients with bacteraemia (84 cases nosocomial) caused by methicillin-resistant Staphylococcus aureus (MRSA). Patients were investigated by means of a standard protocol at a 944-bed hospital in the years 2000–2004. Empiric antibiotic therapies included vancomycin (n = 49), teicoplanin (n = 20), linezolid (n = 17), other antibiotics active in vitro (n = 7), and inactive antibiotics (n = 7). Overall mortality was 40% (12% among linezolid-treated patients; 46.3% among glycopeptide-treated patients). In bivariate analyses, the following factors were statistically associated with higher mortality: rapidly fatal underlying disease, altered mental status, metabolic acidosis, and acute severe clinical condition at the onset of bacteraemia; development of complications (septic shock, renal failure, and disseminated intravascular coagulopathy); empiric monotherapy with glycopeptides (vs combination therapy with an aminoglycoside); and inadequate empiric treatment. Empiric therapy with linezolid was associated with lower mortality. In multivariate analysis, risk factors associated with higher mortality included acute severity of illness (OR 7.49; 95%CI 1.19–25.3) and altered mental status (OR 4.83; 95%CI 1.22–19.15) at onset, complications (OR 3.42; 95%CI 1.02–17.46), and inappropriate empiric treatment (OR 7.6; 95%CI 1.87–31.14). In multivariate analysis limited to patients who received empiric therapy with either linezolid (n = 17) or glycopeptides (n = 69), linezolid was associated with greater rates of survival (OR 7.7; 95%CI 1.1–53) and microbiological eradication (OR 11.76; 95%CI 1.46–90.9) but not with fewer complications (OR 0.71; 95%CI 0.16–3.25). In conclusion, the main prognostic factors associated with mortality in patients with MRSA bacteraemia are complications, acute severe clinical condition at onset, and inappropriate empiric treatment. Empiric therapy with linezolid was associated with greater survival and more successful microbiological eradication but did not reduce complications.     

Clinical predictive values of extended-spectrum beta-lactamase carriage in patients admitted to medical wards

We aimed to reassess, through clinical items, populations at risk for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) carriage at admission to hospital and to assess the risk of further positive clinical culture of ESBL-E among carriers. We performed a 5-month cohort study in a medicine ward of a 500-bed university teaching hospital in the Parisian area of France. All admitted patients were prospectively enrolled for rectal swabbing and clinical data collection, including bacterial infection at admission and during stay. Variables associated with ESBL-E carriage were identified by univariate and multivariate analysis. Five hundred patients were included. The prevalence of ESBL-E was 6.6% (33/500) upon admission. Only previous carriage of multidrug-resistant bacteria (MDRB) was associated with carriage (odds ratio [OR]: 17.7, 95% confidence interval (CI) 5.8–54.2, p < 0.001), yet, the positive predictive value (PPV) was not higher than 50%. When prior MDRB carriage was not considered in the multivariate analysis, only prior antibiotic consumption was found to be associated with carriage at admission (OR: 2.2 [1.1–4.5], p = 0.02). Two patients had ESBL-E infection at admission, yet, no patient became infected with ESBL-E during their stay. The clinical prediction of ESBL carriage at admission in our wards was found to be poorly efficient for assessing the at-risk population.     

Pulmonary <Emphasis Type="Italic">Mycobacterium simiae</Emphasis> infection: comparison with pulmonary tuberculosis

To identify the clinical and radiological features distinguishing Mycobacterium simiae respiratory infection from pulmonary tuberculosis, the demographics, underlying conditions, and clinical and radiological findings of 121 consecutive patients with pulmonary tuberculosis and 102 with M. simiae respiratory infection were compared retrospectively. In the M. simiae group, the patients were older (mean age 69 ± 16 years vs. 47 ± 21 years, p = 0.0001), with a female predominance (62% vs. 45%, p = 0.008). Only 4% were of Ethiopian origin compared to 25% of the tuberculosis group (p = 0.0001). M. simiae infection was associated with significantly higher rates of smoking history, underlying chronic obstructive pulmonary disease, zero human immunodeficiency virus (HIV) infection compared to 10% in the tuberculosis group (p = 0.001), blunted symptoms, and noncavitary infiltrates in the lower/middle lobes on chest X-ray. HIV-negative patients with M. simiae respiratory infection are distinguishable from patients with pulmonary tuberculosis by several demographic, clinical, and radiological features. These findings have important diagnostic and therapeutic implications.     

Relation between Epstein-Barr virus and multiple sclerosis: analytic study of scientific production

Numerous studies have been carried out to determine whether infection by the Epstein-Barr virus (EBV) can be considered as a risk factor for multiple sclerosis (MS). This work is a meta-analysis of case–control observational studies published before January 2009 aimed at assessing the degree of association between EBV and MS infections. A Medline electronic database search was carried out using “Epstein-Barr virus” and “multiple sclerosis” as keywords, from which we selected 30 published studies that met our methodology criteria. We found an association between MS and an exposure to EBV, studied by determining the anti-VCA IgG antibodies (odds ratio [OR] = 5.5; 95% confidence interval [CI] = 3.37–8.81; p < 0.0001), anti-complex EBNA IgG (OR = 5.4; 95% CI = 2.94–9.76; p < 0.0001) and anti-EBNA-1 IgG (OR = 12.1; 95% CI = 3.13–46.89; p < 0.0001). No significant association could be found when studying anti-EA IgG (OR = 1.3; 95% CI = 0.68–2.35; p = 0.457), EBV DNA in serum (OR = 1.8; 95% CI = 0.99–3.36; p = 0.051) and DNA in brain tissues and in cerebrospinal fluid (CSF) (OR = 0.9; 95% CI = 0.38–2.01; p = 0.768). This meta-analysis detected an association between infection by EBV and MS through the investigation of antibodies, mainly anti-EBNA-1, anti-complex EBNA and anti-VCA IgG.     

Short- and long-term outcome of HIV-infected patients admitted to the intensive care unit

The purpose of this investigation was to analyse the impact of the availability of highly active antiretroviral therapy (HAART) on the long-term outcome of human immunodeficiency virus (HIV)-infected patients admitted to the intensive care unit (ICU). A retrospective cohort study of HIV-infected patients admitted to the ICU was undertaken. Outcomes in the pre-HAART era (1990–June 1996), early- (July 1996–2002), and recent-HAART (2003–2008) periods and total HAART era (July 1996–2008) were analysed and compared with those reported of the general population. A total of 127 ICU admissions were included. The 1-year mortality decreased from 71% in the pre-HAART era to 50% in the recent-HAART period (p = 0.06). The 5-year mortality decreased from 87% in the pre-HAART era to 59% in the early-HAART period (p = 0.005). Independent predictors of 1-year mortality in the HAART era were age (odds ratio [OR] = 1.16 [95% confidence interval [CI] = 1.06–1.27]), APACHE II score > 20 (6.04 [1.25–29.22]) and mechanical ventilation (40.01 [3.01–532.65]). The 5-year survival after hospitalisation was 80% and in the range of the reported survival of non-HIV-infected patients (83.7%). Predictors of 1-year mortality for HIV patients admitted to the ICU in the HAART era were all non-HIV-related. Short- and long-term outcome has improved since the introduction of HAART and is comparable to the outcome data in non-HIV-infected ICU patients.