Effect of statins on outcomes in immunosuppressed patients with bloodstream infection

Although it has been suggested that statins have a beneficial effect on the outcome of bloodstream infection (BSI) in immunosuppressed patients, prospective studies testing this hypothesis are lacking. We performed an observational analysis of consecutive cancer patients and transplant recipients hospitalized at two tertiary hospitals in Spain (2006–2009). The first episode of BSI occurring in statin users was compared with those occurring in non-statin users. During the study period, 668 consecutive episodes of BSI in 476 immunosuppressed patients were recorded. Underlying diseases were solid tumor (46.2%), hematologic malignancy (35.1%), and transplantation (18.7%). Fifty-nine (12.4%) patients were receiving statins at the onset of BSI. Comparing with statin non-users, patients on statin treatment were older (67.3 vs. 58.7 years; p < 0.001) and had higher frequency of comorbidities (74.6% vs. 40.6%; p < 0.001). There were no significant differences in intensive care unit admission (6.8% vs. 7.7%; p = 1) and overall mortality (15.3% vs. 24%; p = 0.13) between groups. In a multivariate analysis, prior statin use was not associated with increased survival (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.22–1.23; p = 0.14). In conclusion, prior statin use is not associated with increased survival in immunosuppressed patients with BSI. Caution is warranted in attributing beneficial effects to statin use in infections among immunocompromised patients.     

Effects on spectrum and susceptibility patterns of isolates causing bloodstream infection by restriction of fluoroquinolone prophylaxis in a hematology–oncology unit

The emergence of fluoroquinolone-resistant gram-negative organisms has been demonstrated in patients given fluoroquinolone prophylaxis. To prevent increases in resistant bacteria, we restricted prophylactic use of fluoroquinolones. The spectrum and susceptibility patterns of isolates causing bloodstream infection (BSI) were assessed in patients receiving chemotherapy during periods of routine prophylaxis (period A: October 2001 to May 2003) and restricted prophylaxis (period B: June 2003 to January 2005). The total number of patients receiving chemotherapy was 442 during period A and 365 during period B. No significant differences were seen between periods with respect to patient characteristics. BSI was identified in 42 patients (44 episodes) during period A and 69 patients (74 episodes) during period B. Incidence of BSI increased significantly from 10.0% (44/442) during period A to 20.3% (74/365) during period B (P < 0.0001). Rate of Enterobacteriaceae BSI increased significantly, from 2.0% (9/442) during period A to 8.2% (30/365) during period B (P < 0.0001). For all BSI episodes, the proportion of BSI with gram-positive cocci decreased from 63.6% (28/44) during period A to 44.6% (33/74) during period B (P = 0.045), while the proportion of BSI with Enterobacteriaceae increased from 20.5% (9/44) to 40.5% (30/74) (P < 0.0001). The proportion of fluoroquinolone-resistant Enterobacteriaceae BSI for all Enterobacteriaceae BSI decreased from 75% (9/12) during period A to 17% (5/30) during period B (P = 0.0078). Restriction of fluoroquinolone prophylaxis affects the etiology of BSI and reduces the proportion of drug-resistant organisms.     

Statins are associated with improved outcomes of bloodstream infection in solid-organ transplant recipients

Among recipients of intra-abdominal solid-organ transplants, bloodstream infections (BSIs) are a major cause of mortality. We undertook a retrospective cohort study of recipients of kidney, pancreas, and/or liver transplants with BSIs at a single center over an 11-year period. Multivariate analysis using logistic regression was used to determine independent predictors of 15-day mortality and clinical cure, with a focus on the use of statins. Three hundred and eleven recipients of solid-organ transplants had 604 episodes of BSI. Forty-four (14%) died within 15 days of BSI. Sixteen percent did not achieve clinical cure. In the multivariate model, each one point increase in the APACHE score was associated with a 1.09-fold increased risk of death (95% confidence interval [CI] 1.00–1.18, P = 0.03). The lack of appropriate antibiotic therapy was associated with a four-fold higher risk of death within 15 days (odds ratio [OR] 4.65, 95% CI 1.46–14.78, P = 0.009). Statin use was protective (OR 0.18, 95% CI 0.04–0.78). Patients with high APACHE scores, nosocomial rather than community source of BSI, lack of appropriate antibiotic therapy, and mental status changes were less likely to achieve clinical cure of their BSIs. In conclusion, appropriate antibiotic therapy and statin use are associated with lower risk of mortality from BSIs in this patient population.     

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.     

Clinical characteristics and outcomes of patients with vancomycin-susceptible Enterococcus faecalis and Enterococcus faecium bacteraemia in cancer patients

The purpose of this investigation was to compare the risk factors, clinical features and outcomes in cancer patients with bacteraemia caused by vancomycin-susceptible Enterococcus faecalis and E. faecium. A retrospective, observational 7-year study was carried out in a 450-bed, acute-care university-affiliated hospital. We performed univariate comparisons between the two groups and then multivariate analysis to identify patient risk factors for E. faecium isolation. Seventy-three patients were included in the analysis: 54 (74.0%) with bacteraemia caused by E. faecalis and 19 (26.0%) by E. faecium. The Simplified Acute Physiological Score (SAPS) value was significantly greater in E. faecium isolates (40.7 vs. 35.2; p = 0.009). Diabetes mellitus was more frequently diagnosed in patients with E. faecium bacteraemia (52.6% vs. 24.1%; p = 0.021). Prior penicillin exposure was more frequent in patients with E. faecium bacteraemia (68.4% vs. 29.6%; p = 0.003). There was a trend toward higher mortality in E. faecium bacteraemia patients (47.4% vs. 25.9%; p = 0.084). Independent patient risk factors for E. faecium isolation were prior penicillin exposure (odds ratio [OR], 6.479; p = 0.003) and SAPS > 34 (OR, 6.896; p = 0.009). When compared to E. faecalis bacteraemia, E. faecium bacteraemia in cancer patients is independently associated with more severe illness and prior use of penicillins; therefore, empiric treatment which would cover E. faecium should be considered in cancer patients suspected of having bacteraemia.     

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.     

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.     

Impact of healthcare-associated acquisition on community-onset Gram-negative bloodstream infection: a population-based study

We performed a population-based study to examine the influence of healthcare-associated acquisition on pathogen distribution, antimicrobial resistance, short- and long-term mortality of community-onset Gram-negative bloodstream infections (BSI). We identified 733 unique patients with community-onset Gram-negative BSI (306 healthcare-associated and 427 community-acquired) among Olmsted County, Minnesota, residents from 1 January 1998 to 31 December 2007. Multivariate logistic regression was used to examine the association between healthcare-associated acquisition and microbiological etiology and antimicrobial resistance. Multivariate Cox proportional hazards regression was used to evaluate the influence of the site of acquisition on mortality. Healthcare-associated acquisition was predictive of Pseudomonas aeruginosa (odds ratio [OR] 3.14, 95% confidence intervals [CI]: 1.59–6.57) and the group of Enterobacter, Citrobacter, and Serratia species (OR 2.23, 95% CI: 1.21–4.21) as causative pathogens of community-onset Gram-negative BSI. Healthcare-associated acquisition was also predictive of fluoroquinolone resistance among community-onset Gram-negative bloodstream isolates (OR 2.27, 95% CI: 1.18–4.53). Healthcare-associated acquisition of BSI was independently associated with higher 28-day (hazard ratio [HR] 3.73, 95% CI: 2.13–6.93) and 1-year mortality (HR 3.60, 95% CI: 2.57–5.15). Because of differences in pathogen distribution, antimicrobial resistance, and outcomes between healthcare-associated and community-acquired Gram-negative BSI, identification of patients with healthcare-associated acquisition of BSI is essential to optimize empiric antimicrobial therapy.     

Clinical features,antimicrobial susceptibilities,and outcomes of <Emphasis Type="Italic">Elizabethkingia meningoseptica</Emphasis> (<Emphasis Type="Italic">Chryseobacterium meningosepticum</Emphasis>) bacteremia at a medical center in Taiwan, 1999–2006

A total of 118 patients with Elizabethkingia meningoseptica bacteremia at a medical center in Taiwan from 1999 to 2006 were studied. Minimum inhibitory concentrations (MICs) of 99 preserved isolates were determined. The incidence (per 100,000 admissions) of E. meningoseptica bacteremia increased from 7.5 in 1996 to 35.6 in 2006 (p = 0.006). Among them, 84% presented with fever, 86% had nosocomial infections, and 60% had acquired the infection in intensive care units (ICUs). The most common underlying diseases were malignancy (36%) and diabetes mellitus (25%). Seventy-eight percent of patients had primary bacteremia, followed by pneumonia (9%), soft tissue infection, and catheter-related bacteremia (6%). Forty-five patients (38%) had polymicrobial bacteremia. Overall, the 14-day mortality was 23.4%. Multivariate analysis revealed E. meningoseptica bacteremia acquired in an ICU (p = 0.048, odds ratio [OR] 4.23) and presence of effective antibiotic treatment after the availability of culture results (p = 0.049, OR 0.31) were independent predictors of 14-day mortality. The 14-day mortality was higher among patients receiving carbapenems (p = 0.046) than fluoroquinolones or other antimicrobial agents. More than 80% of the isolates tested were susceptible to trimethoprim-sulfamethoxzole, moxifloxacin, and levofloxacin. The MIC₅₀ and MIC₉₀ of the isolates to tigecycline and doxycycline were both 4 μg/mL and 8 μg/ml, respectively.     

Epidemiology of Nosocomial Bloodstream Infections in Belgium, 1992–1996

 The main results of the bloodstream infection (BSI) component of the Belgian National Programme for the Surveillance of Hospital Infections (NSIH project) are reported. From October 1992 to September 1996, 117 hospitals (59.1% of Belgian acute-care institutions) reported 13 678 nosocomial BSIs. The incidence was 7.05 BSI episodes per 10 000 patient-days. The incidence of BSI increased with hospital size and over time. Bloodstream infections were secondary to an infectious body site in 40.3% of the episodes, catheter-related in 23.5%, and of unknown origin in 36.2%. The associated in-hospital mortality was 31.4% and was highest in BSIs secondary to a respiratory tract infection (49.3%). In intensive care units, the incidence of BSI was 38.5 per 10 000 patient-days. Coagulase-negative staphylococci were the most prevalent microorganisms (22%), followed by Staphylococcus aureus (14.1%) and Escherichia coli (13.5%). In catheter-related BSIs, these proportions were 41.9%, 18.8%, and 2.3%, respectively. The proportion of polymicrobial episodes was 9.9%. Methicillin resistance in Staphylococcus aureus was 22.3%. With its high participation rate, the NSIH project has characterized the epidemiology of nosocomial BSIs in Belgium during the period studied.     

Cefotaxime resistance and outcome of Klebsiella spp bloodstream infection

We attempt to describe the epidemiology and outcome associated with cefotaxime-resistant (CTX-R) Klebsiella spp bacteraemia. Klebsiella spp bloodstream infection episodes prospectively collected through a blood culture surveillance programme from January 1991 to December 2008 in a single institution were analysed. A total of 910 monomicrobial episodes of Klebsiella spp bacteraemia were identified during the study period. The most important sources were from urinary tract infection, unknown sources, billiary focus and catheter related infection. There were 112 (12%) CTX-R isolates. Out of 112 isolates, 98 were CTX-R by Extended-Spectrum β-Lactamase production. Shock on presentation and mortality were significantly more frequent in CTX-R than in CTX susceptible isolates. Inappropriate empirical therapy was received in 50 (45%) cases in the CTX-R Klebsiella spp group (13 cases of death, 26%). Predictive factors associated with CTX-R Klebsiella spp isolate were: previous β-lactam therapy (OR = 4.16), nosocomial acquired bacteraemia (OR = 1.93), solid organ trasplantation (OR = 2.09) and shock (OR = 1.90). Independent risk factors associated with mortality in Klebsiella spp bacteraemia were: age (OR = 1.03), liver cirrhosis (OR = 2.63), ultimately or rapidly fatal prognosis of underlying disease (OR = 2.44), shock (OR = 8.60), pneumonia (OR = 4.96) or intraabdominal (OR = 3.85) source of bacteraemia and CTX-R isolate (OR = 4.63). Klebsiella spp is an important cause of bloodstream infection. CTX-R isolates have been increasing since 2000. CTX-R is an independent factor associated with mortality in Klebsiella spp bacteraemia.     

Blood drawn through valved catheter hub connectors carries a significant risk of contamination

Infection Control became concerned when bloodstream infection (BSI) rates increased after implementing a needleless valved hub connector. During a 21-month period three different needleless catheter hub connectors were evaluated by quantitatively culturing blood drawn through hub connectors that would have ordinarily been discarded (DBC). DBC drawn through Clearlink™ catheter hub connectors were found to be twice as likely to be positive as DBC drawn through Clave? or Q-syte™ hub connectors (P < 0.04). DBC grew pathogens 46% of the time and skin organisms 54% of the time. Patients with positive DBC were three times more likely to meet Centers for Disease Control (CDC) BSI criteria by DBC cultures than by physician-ordered blood cultures (CBC; P < 0.001). For patients growing pathogens in DBC, 64% had no CBC drawn, the average temperature was lower than for patients with pathogens in CBC (99.3 ± 1.5 ve 100.6 ± 1.9, P = 0.015), and 92% of discharged patients (11 out of 12) were not treated with an antibiotic active against the DBC pathogen. Drawing BC through a catheter hub connector carries a risk of false-positives that could increase BSI rates by up to 3-fold. Further work is necessary to evaluate this concern.     

Risk factors for multidrug-resistant tuberculosis in a tuberculosis unit in Madrid,Spain

The setting for this retrospective cohort study was a specialised tuberculosis unit in Madrid, Spain. The objective was to describe the risk factors for multidrug-resistant tuberculosis (MDR-TB). The medical records of all patients admitted to the unit were reviewed retrospectively to identify factors associated with multidrug resistance. Patients with positive culture for M. tuberculosis and with available drug-susceptibility tests were included. The variables assessed were age, gender, country of origin, homelessness, alcohol consumption, intravenous drug use, methadone substitution therapy, contact with a tuberculosis patient, sputum smear, site of disease, previous tuberculosis treatment, HIV infection, history of imprisonment, diabetes mellitus and chronic obstructive pulmonary disease. Thirty patients with MDR-TB and 666 patients with non-MDR-TB were included from the years 1997 to 2006. The only factors associated with MDR-TB in multivariate analysis were previous tuberculosis treatment (OR: 3.44; 95% CI: 1.58–7.50; p = 0.003), age group 45–64 years (OR: 3.24; 95% CI: 1.34–7.81; p = 0.009) and alcohol abuse (OR: 0.12; 95% CI: 0.03 to 0.55; p = 0.003). In our study, patients who had had previous treatment for tuberculosis, who were 45–64 years of age or who had no history of alcohol abuse were more likely to have MDR-TB.     

Epidemiology of Streptococcus pneumoniae and Staphylococcus aureus colonization in healthy Venezuelan children

Streptococcus pneumoniae and Staphylococcus aureus cause significant morbidity and mortality worldwide. We investigated both the colonization and co-colonization characteristics for these pathogens among 250 healthy children from 2 to 5 years of age in Merida, Venezuela, in 2007. The prevalence of S. pneumoniae colonization, S. aureus colonization, and S. pneumoniae–S. aureus co-colonization was 28%, 56%, and 16%, respectively. Pneumococcal serotypes 6B (14%), 19F (12%), 23F (12%), 15 (9%), 6A (8%), 11 (8%), 23A (6%), and 34 (6%) were the most prevalent. Non-respiratory atopy was a risk factor for S. aureus colonization (p = 0.017). Vaccine serotypes were negatively associated with preceding respiratory infection (p = 0.02) and with S. aureus colonization (p = 0.03). We observed a high prevalence of pneumococcal resistance against trimethoprim–sulfamethoxazole (40%), erythromycin (38%), and penicillin (14%). Semi-quantitative measurement of pneumococcal colonization density showed that children with young siblings and low socioeconomic status were more densely colonized (p = 0.02 and p = 0.02, respectively). In contrast, trimethoprim–sulfamethoxazole- and multidrug-resistant-pneumococci colonized children sparsely (p = 0.03 and p = 0.01, respectively). Our data form an important basis to monitor the future impact of pneumococcal vaccination on bacterial colonization, as well as to recommend a rationalized and restrictive antimicrobial use in our community.     

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.     

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.     

Comparison of mortality between nosocomial and community-acquired febrile neutropenia patients treated initially with cefazolin plus tobramycin: retrospective chart review

Cefazolin plus tobramycin have been determined to be effective for community-acquired FN, but have not been evaluated in the treatment of nosocomial FN. This study compared the incidence of mortality from 2002 to 2004 with 2008 to 2009 in patients with nosocomial FN treated with cefazolin plus tobramycin and compared characteristics of patients with nosocomially acquired FN to community acquired FN. A retrospective chart review of 45 nosocomial FN episodes from 2008 to 2009, and 54 episodes from 2002 to 2004 treated with cefazolin plus tobramycin was conducted. Data on the community acquired FN episodes was obtained from our previous research. Nosocomial FN mortality increased from 4% in 2002–2004 to 13% in 2008–2009 (p = 0.08). The nosocomial cohort was at higher risk of medical complications and mortality than the community-acquired cohort based on several variables (neutrophil nadir, duration of neutropenia and fever, hematological malignancy, MASCC and Talcott score; p < 0.05). As a result, the nosocomial cohort was treated with longer courses of antibiotic therapy (14 days vs 7 days; p < 0.0001) and were more likely to require broader spectrum antibiotics (64 out of 99 vs 34 out of 96; p < 0.0001). There was an observed increased risk of mortality from 2002 to 2004 compared with 2008 to 2009 in patients treated with cefazolin plus tobramycin for nosocomial FN, this was notable despite not attaining statistical significance. Therefore, this regimen is not appropriate for nosocomial FN.     

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.     

Epidemiology and outcomes of bloodstream infections in 177 severe burn patients from an industrial disaster: a multicentre retrospective study

ObjectivesTo determine the characteristics of bloodstream infections (BSIs) and to evaluate the impact of BSIs on mortality in severe burn patients.MethodsA retrospective observational study was conducted in 20 tertiary hospitals. A total of 185 patients who experienced a massive dust explosion in eastern China were included.ResultsAfter exclusion, 177 patients were analysed. The median total body surface area (TBSA) burned was 95% (interquartile range 85%–98%). Inhalation injuries occurred in 97.2%. The overall 90-day mortality was 35% (62/177). During the study period, 120 (67.8%) patients developed 253 episodes of BSI with 323 unique causative pathogens. Sixty-six episodes were polymicrobial infections. Catheter-related BSIs (CRBSIs) accounted for 41.5% of the episodes. Acinetobacter baumannii (19.5%), Klebsiella pneumoniae (13.9%) and Candida (12.7%) were the most common organisms. Antimicrobial resistance was found in 63.5% of the isolates, particularly in Gram-negative bacteria. Patients who developed BSIs had a greater illness severity at admission to the intensive care unit, and worse outcomes. After adjusting for demographics, severity of illness and treatment characteristics in a multivariate logistic model, there was a trend toward BSI increasing the risk of 90-day mortality (adjusted OR 3.4; 95% CI 0.9–12.9; p=0.069). In subgroup analyses, CRBSIs (adjusted OR 5.7; 95% CI 1.3–24.9; p=0.021 versus no BSI) and polymicrobial BSIs (adjusted OR 6.1; 95% CI 1.3–28.1; p=0.020 versus no BSI) had greater risk of 90-day mortality.ConclusionsA strikingly high rate of BSIs was observed in severe burn patients. Gram-negative organisms and fungi were the leading causes. CRBSIs and polymicrobial BSIs were associated with high mortality.     

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.