Analysis of Risk Factors for Ventilator-Associated Pneumonia in a Multidisciplinary Intensive Care Unit

 A prospective study was conducted to determine the incidence, risk factors and pathogens of ventilator-associated pneumonia (VAP) in 198 patients requiring mechanical ventilation for more than 48 hours. VAP occurred in 67 (33.8%) patients. Risk factors associated with VAP were admission APACHE II score >20 (odds ratio [OR] 4.77, 95% confidence interval [CI] 2.04–11.27, P<0.001), mechanical ventilation >10 days (OR 44.4, 95% CI 2.16–26.7, P<0.0001), ICU length of stay >10 days (OR 9.4, 95% CI 3.55–25.65, P<0.0001), and admission PaO₂/FiO₂ ratio <200 mmHg (OR 3.4, 95% CI 1.00–11.41, P<0.05). Logistic regression analysis showed a relationship between VAP and length of stay in ICU, duration of fever and presence of catheter-related infection. The pathogens isolated were predominantly gram-negative bacteria (83.2%), with a high proportion of Acinetobacter spp. (35%) resistant to commonly used antimicrobial agents. The mortality rate was not influenced by VAP.     

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.     

Seroprevalence of Toxoplasma gondii infection among immigrant and native pregnant women in Eastern Spain

In European countries, toxoplasma antenatal screening is recommended to prevent toxoplasmosis. The seroprevalence of these infections in immigrants can be different than in native population. From February 2006 to June 2010, a cross-sectional study was carried out in all pregnant women attended at a reference unit in Elche, Spain. An enzyme immunoassay was used for detection of IgG antibodies against Toxoplasma gondii. For each immigrant woman, one Spanish pregnant woman of the same age cared for in the same day was recruited (Spanish control group). A total of 1,627 migrant pregnant women participated in this study. The adherence to screening among migrants was 91.9% (95% CI, 90.5–93.1%), similar than that found in Spaniards (92.2%; 95% CI, 90.8–93-4%). Among migrant women, 619 were positive for IgG anti-T. gondii antibodies (41.4%; 95% CI, 38.9–43.9%), compared with 12.0% (95% CI, 10.5–13.8%) among Spaniards (odds ratio (OR), 5.2 (95% CI, 4.3–6.3). Seroprevalence in pregnant women from Latin America, northern Africa, Eastern Europe, Africa Sub-Saharan and Western Europe was higher than in the Spanish control group (OR, 5.4, 5.8, 6.5, 5.4, and 2.4, respectively; p < 0.001). No Asian pregnant woman was immune. Seroprevalence increased with increasing age in migrant pregnant women: 15–25 years, 38.2%; 26–35 years, 40.7%; and 36–45 years, 52.8%. The seroprevalence of T. gondii infection in migrant pregnant women living in Spain was higher than in the native population. However, no cases were found in Asian immigrants, highlighting the importance of primary prevention of this infection in pregnant women coming from that geographic region.     

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.     

<Emphasis Type="Italic">Toxoplasma gondii</Emphasis> antibody profile in HIV-infected pregnant women and the risk of congenital toxoplasmosis

The purpose of this study was to investigate the antibodies to Toxoplasma gondii in human immunodeficiency virus (HIV)-infected pregnant women and to determine the association between serological profile and the risk of congenital toxoplasmosis. The study, conducted in a public maternity ward from May 2002 to April 2005, included all HIV-infected women who delivered live infants during the 36 months, and, as a control group, all HIV-negative women that delivered live infants in the first 12 months of the study. Antibodies to T. gondii were detected in 1,624 of 2,421 HIV-negative women (67%; 95% confidence interval [CI] 65–69%) and in 121 of 168 HIV-infected patients (72%; 95% CI 65–79%). A total of 547 HIV-negative and 103 HIV-infected patients were tested at delivery and had positive T. gondii-specific IgG. In HIV-negative women, the median of the specific IgG concentration was 79 (interquartile range 38–160), and in HIV-infected patients, it was 283 (interquartile range 94–704) (P < 0.001). In the group of co-infected women, the only infant with congenital toxoplasmosis was born to a mother with acute toxoplasmosis infection acquired during pregnancy who did not have a high specific IgG concentration or a positive result for specific IgM. We concluded that high T. gondii-specific IgG values were much more frequent among HIV-infected pregnant women, but it did not translate into an increased risk of maternal–fetal transmission of toxoplasmosis.     

Risk Factors for Catheter-Associated Bacteriuria in a Medical Intensive Care Unit

 In a prospective study including 137 consecutive catheterised patients in a medical intensive care unit, the following variables were analysed as possible risk factors for catheter-associated bacteriuria, defined as a quantitative culture with ≥10⁵ organisms/ml: age, sex, simplified acute and physiologic score at admission, duration of catheterisation, diabetes mellitus, immunosuppression, neurologic disorders and prior systemic antibiotic exposure during hospitalisation. The frequency of catheter-associated bacteriuria was 30.7%. By multivariate analysis, female sex (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.9–13.5;P=0.001) and a duration of catheterisation  1 11 days (OR, 19.4; 95% CI, 5.5–68.7;P=0.0001) were risk factors for catheter-associated bacteriuria, and prior antibiotic exposure was a protective factor (OR, 0.06; 95% CI, 0.019–0.21;P=0.0001).     

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.     

Inhaled aminoglycosides in cancer patients with ventilator-associated Gram-negative bacterial pneumonia: safety and feasibility in the era of escalating drug resistance

We sought to evaluate the safety and feasibility of inhaled aminoglycosides or colistin in cancer patients with ventilator-associated pneumonia (VAP) due to Gram-negative bacteria (GNB). A retrospective case-matched study was obtained after obtaining IRB approval in patients at the intensive care unit at our NCI-designated comprehensive cancer center between 1999 and 2005. Sixteen patients with GNB-VAP who received inhaled aminoglycosides or colistin were compared with 16 patients who had received these antibiotics intravenously alone. Eligible patients were required to have received at least six doses of inhaled therapy, or 3 or more days of intravenous therapy. Clinical Pulmonary Infection Scores were used to assess pneumonia severity. Standard ATS criteria were used to define VAP. Patients treated with inhaled antibiotics were less likely to have received corticosteroids (13% vs 50%; P < 0.02) and had a higher median baseline creatinine level (0.85 vs 0.6 mg/dL; P < 0.02) than patients treated intravenously. Pseudomonas aeruginosa (69%) was the most common cause of VAP. There were no serious adverse events associated with inhaled antibiotics. Patients who received these antibiotics intravenously developed renal dysfunction (31%); none of the patients treated with inhaled antibiotics developed nephrotoxicity (P ≤ 0.04). Patients treated with inhaled antibiotics were more likely to have complete resolution of clinical (81% vs 31% in the intravenous antibiotic group; P < 0.01) and microbiologic infection (77% vs 8% in the intravenous antibiotic group: P < 0.0006). In a multivariate analysis adjusted for corticosteroid use, inhaled antibiotic therapy was predictive of complete clinical resolution (odds ratio [OR], 6.3; 95% confidence interval [CI], 1.1, 37.6; P < 0.04) and eradication of causative organisms (OR 36.7; 95% CI, 3.3, 412.2; P < 0.003). In critically ill cancer patients with Gram-negative VAP, inhaled aminoglycosides were tolerated without serious toxicity and may lead to improved outcome. A portion of this study was presented at the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, 27–30 September 2006, San Francisco [abstract K-0288].     

Seroprevalence and sources of Toxoplasma infection among indigenous and immigrant pregnant women in Taiwan

Investigation on seroprevalence and risk factors of Toxoplasma gondii infections among indigenous and immigrant pregnant women in Mid-Taiwan showed that anti Taxoplasma-specific IgG antibody counts were significantly higher in indigenes (40.6%) than in immigrants (18.2%), with an odds ratio of OR = 3.34 (95% CI: 1.93–4.80). The titre of Taxoplasma-specific IgG was also significantly higher in indigenes than in immigrants (P < 0.001). Differences of living styles for Toxoplasma infection between the two groups were drinking untreated water (OR = 2.34, 95% CI: 1.36–4.02), consumption of raw/undercooked meats (OR = 10.11 95% CI: 4.92–20.78), especially raw/undercooked pork (P = 0.000), or raw/undercooked viscera (OR = 9.16, 95% CI: 2.97–27.94), contact with cats (OR = 5.69, 95% CI: 2.83–11.47), or soil (OR = 2.55 95% CI: 1.72–3.80). Differences of risk factors for Toxoplasma infection in terms of positive IgG in the two groups were consumption of raw/undercooked meats (P = 0.005) especially raw/undercooked pork (P = 0.004), and contact with cats (P = 0.013) or soil (P = 0.028). It is concluded that seroprevalence of Toxoplasma infection is higher in indigenous pregnant women and related to their living styles. To prevent congenital toxoplasmosis, health education seems required.     

Prevalence of heterophyiosis in Tilapia fish and humans in Northern Egypt

A total of 100 Tilapia fish samples were collected from brackish water (n = 50) and fresh water (n = 50) resources, Northern Egypt, and examined for heterophyid encysted metacercariae (EMC) during the period from August 2007 to July 2008. The overall prevalence of infection was 32%; 22% for brackish water fish and 42% for fresh water fish. Significant differences in parasite occurrence among body regions were found, with muscles of the tail and caudal third being highly affected (93.4%) followed by middle third (84.3%) and anterior third (75%), while the head region had the lowest infection (21.9%). The prevalence was highest in summer season (46.4%) followed by spring (37.5%) and autumn (27.3%), and was lowest in winter (15.4%). The prevalence of infection decreased as fish size increased. Adult heterophyids, Heterophyes heterophyes, Heterophyes aequalis, Pygidiopsis genata, Haplorchis yokogawai, and Ascocotyle (Phagicola) ascolonga were recovered from EMC-feed puppies. Eggs of heterophyid type were detected in 10 (13.3%) out of 75 human stool specimens from local residents. An association exists between being a female (odd ratio [OR] 1.59 and 95% confidence interval [CI] 0.42–6.04), a fisherman (OR 1.39 [95% CI 0.26–7.48]), a housewife (OR 1.24 [95% CI 0.29–6.28]), 15–45 years old (OR 2.22 [95% CI 0.58–8.53]), or aged 5–14 years (OR 1.29 [95% CI 0.30–5.58]) and heterophyid infection. Measures should be implemented to reduce the risk of transmission of heterophyids to human and fish-eating animals.     

Different roles of MTHFR C677T and A1298C polymorphisms in colorectal adenoma and colorectal cancer: a meta-analysis

Association studies on the MTHFR polymorphisms (C677T and A1298C) in colorectal cancer (CRC) and colorectal adenoma have shown conflicting results. We performed a meta-analysis to better assess the purported associations. Overall, the 677T allele (10,131 patients and 15,362 controls) showed a small but significant protective effect against CRC compared to the 677C allele [P=0.0003, odds ratio (OR)=0.93; 95% confidence interval (CI) 0.89–0.98, P=0.22 (for heterogeneity)] for a worldwide population. Meta-analyses of other genetic contrasts suggested that the 677T allele is more likely to affect CRC in a recessive genetic model worldwide (P<0.0001, OR=0.86; 95% CI 0.76–0.96, P=0.06) and in Asians (P=0.0005, OR=0.75; 95% CI 0.64–0.88, P=0.71). Similarly, we found a significantly decreased risk of CRC for 1298C polymorphism (4,764 CRC patients and 6,592 controls) for a recessive genetic model worldwide (P=0.005, OR=0.81; 95% CI 0.70–0.94, P=0.40) and in Caucasians (P=0.04, OR=0.75 95% CI 0.57–0.99, P=0.35). No evidence of association of C677T (4,616 patients and 6,338 controls) and A1298C (1,272 patients and 1,684 controls) with colorectal adenoma were found. The evidence accumulated suggests that MTHFR may represent a low-penetrance susceptible gene for CRC, and that the two polymorphisms might protect against colorectal adenoma developing into cancer. A larger single study is required to further evaluate gene–gene and gene–environment interactions for MTHFR polymorphisms and the cancer risk in a specific population. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

Influence of tracheostomy on the incidence of central venous catheter-related bacteremia

Although there are many studies on catheter-related infection, there are scarce data about the influence of tracheostomy in the incidence of central venous catheter-related bacteremia (CRB). In this cohort study, we found a higher incidence of CRB in patients with tracheostomy than without (11.25 vs. 1.43 per 1,000 catheter-days; odds ratio [OR] = 7.99; 95% confidence interval [CI] = 4.38–infinite; P < 0.001). Besides, we found a higher incidence of CRB in patients with tracheostomy using the jugular access compared to subclavian access (21.64 vs. 5.11 per 1,000 catheter-days; OR = 4.23; 95% CI = 1.44–infinite; P = 0.0097).     

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.     

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.     

Proinflammatory cytokine polymorphisms and the risk of preterm birth and low birthweight in a Japanese population

Pregnancy and parturition involve a complex and poorly understoodmolecular and biological interplay between mother and fetus.Inflammatory cytokines have been reported to be associated withfetal growth and parturition. The aim of this study was to examinewhether common proinflammatory cytokine polymorphisms are associatedwith preterm birth (PTB), low birthweight or intrauterine growthrestriction in a Japanese population. We assessed a consecutiveseries of 414 women who had singleton deliveries in Sapporo,Japan between 2001 and 2005. Genotyping of IL1A –889C/T,+4845G/T (A114S), IL1B –511C/T, –31C/T, IL2 –384T/Gand IL6 –634C/G polymorphisms was determined by an allelicdiscrimination assay. The risk of PTB significantly increasedin women carrying the IL1A –889T allele (CC genotype [reference];CT genotype, odds ratios (OR): 2.5; 95% confidence intervals(95% CI): 1.4–4.8; CT+TT genotypes [dominant genotypemodel], OR: 2.5, 95% CI: 1.3–4.6). Similarly, the riskof PTB significantly increased in women carrying the IL1A +4845Tallele (GG genotype [reference]; GT genotype, OR: 2.4, 95% CI:1.3–4.4; GT+TT genotypes [dominant genotype model], OR:2.3, 95% CI: 1.2–4.2). The frequency of the IL1A TT haplotypein mothers with PTB was significantly higher than in motherswho had a term birth (P < 0.001), whereas the frequency ofthe IL1A CG haplotype in mothers who had a PTB was significantlylower (P < 0.001). Our findings suggest that the polymorphismsand haplotypes in the IL1A gene are associated with PTB in Japanesewomen.     

Occurrence of antibodies anti-Neospora caninum, anti-Toxoplasma gondii, and anti-Leishmania chagasi in serum of dogs from Pará State, Amazon, Brazil

A cross-sectional study was conducted to determine the occurrence of anti-Toxoplasma gondii, anti-Neospora caninum, and anti- Leishmania chagasi antibodies in dogs of the state of Pará, Brazil. For this purpose, 129 blood samples were collected from dogs of different ages and gender. Samples of 72 dogs were collected from 39 rural properties from 19 municipalities, and 57 samples were from stray dogs, collected after captivity by the Center of Zoonosis Control from the municipality of Santarém. The sera were analyzed for anti-T. gondii and anti-N. caninum antibodies by indirect fluorescent antibody tests with cutoff values of 1:16 and 1:50, respectively. For the presence of L. chagasi antibodies, enzyme-linked immunosorbent assay was used and positive results were confirmed by immunochromatographic method using the recombinant antigen K39. Of the total of 129 dogs, 90 (69.8%) were positive for T. gondii, 16 (12.4%) for N. caninum, and 30 (23.3%) for L. chagasi. Antibodies for all three parasites were found simultaneously in seven dogs (5.4%), mostly in urban dogs (six of seven). No association was observed related to gender and location (urban or rural) of dogs and occurrence of N. caninum and T. gondii antibodies although, regarding L. chagasi, higher prevalence was found in females (P < 0.02) and in dogs from urban location (P < 0.001). From the 39 farms, in 30 (76.9%) at least one dog was positive for T. gondii or N. caninum or both. Higher occurrence of Leishmania antibodies was observed in N. caninum-negative dogs (P < 0.05).     

Incidence and Risk Factors for Nosocomial Infections Caused by Fluoroquinolone-Resistant<Emphasis Type="Italic"> Escherichia coli</Emphasis>

The aim of the retrospective case-control study presented here was to elucidate the incidence, risk factors, and outcomes of nosocomial infections caused by quinolone-resistant Escherichia coli (QREC). During the 3-year period studied, 51 nosocomial QREC infections were found, and the characteristics of these cases were compared with those of 102 control patients with quinolone-susceptible nosocomial infections. In the multivariate analysis, risk factors were identified as prior quinolone therapy (odds ratio [OR], 18.49; 95% confidence interval [CI], 5.53–61.82; P value <0.001), urinary tract abnormalities (OR, 6.69; 95% CI, 1.68–26.63; P=0.007), and prior therapy with other antimicrobial agents (OR, 3.57; 95% CI, 1.38–9.27; P=0.009). No difference in mortality or in length of hospital stay was found. Prudent use of quinolones, especially in patients with urinary tract abnormalities, is probably the best way to avoid an increase in the incidence of QREC infections, but further studies on interventions with restricted use of quinolones are necessary to demonstrate the effectiveness and safety of this strategy.     

Obesity-dependent association of TNF-LTA locus with type 2 diabetes in North Indians

Six common genetic variants (rs2229094, rs1041981, rs1800630, rs1800629, rs361525, and rs1800610) in the TNF-LTA locus encoding the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and lymphotoxin-α have been shown to be associated with various metabolic traits including susceptibility to type 2 diabetes, metabolic syndrome, insulin resistance, and increased body mass index (BMI) in Caucasians from different geographic locations and have yielded mixed results. We tested for the association of these variants with type 2 diabetes in North Indians by studying 2,115 participants comprising of 1,073 type 2 diabetes patients and 1,042 controls. We report the association of a promoter region variant of TNF: rs1800630 and non-synonymous LTA variant: rs2229094 with type 2 diabetes [OR = 0.83 (95% CI 0.72–0.95), P = 0.005 and OR = 0.86 (95% CI 0.75–0.98), P = 0.02, respectively]. Although these associations were BMI-dependent, no interactive effect of BMI and variants on type 2 diabetes was detectable. Further, the haplotype carrying all the six major alleles conferred susceptibility to type 2 diabetes [OR = 1.23 (95% CI 1.06–1.42), P = 0.005; P _permuted = 0.02], with the effect much enhanced in non-obese subjects [OR = 1.45 (95% CI 1.19–1.78), P = 2 × 10⁻⁴: P _permuted = 3 × 10⁻⁴]. The minor allele of rs2229094 was associated with lower hsCRP, BMI, and waist circumference (WC), while the minor allele of rs1800630 showed association with lower BMI and WC (all P < 0.01). This is the first report demonstrating association of rs1800630 and rs2229094 with type 2 diabetes in any population, suggesting an important role of the TNF-LTA locus in type 2 diabetes in North Indians.     

Antibody response of HIV-infected patients to latent,cerebral and recently acquired toxoplasmosis

The aim of this longitudinal study with 626 HIV-infected patients was to evaluate the capability of serological tests in diagnosing the presence of Toxoplasma gondii infection in HIV-infected patients, as well as the potential impact of various treatment regimes on serological results. Low IgG antibody levels and stable or declining titres predominated. IgM positivity occurred in ten patients (one seroconversion, seven latent, two cerebral toxoplasmosis). Complement fixation test (CFT) titres ≥1:32 imply that the relative risk of cerebral toxoplasmosis is 6.84 (95% confidence interval [CI] 1.44–32.5) but with a predictive value of only 14.0% (95% CI 5.3–27.9). Values of specific antibodies are not biassed by antiretroviral treatment and/or prophylaxis for toxoplasmosis, and the detection of specific antibodies is very useful in the identification of T. gondii infection in the HIV-infected population, but the role of serology in predicting the clinical manifestation of T. gondii infection is limited.     

<Emphasis Type="Italic">Aspergillus</Emphasis> infection in lung transplant patients: incidence and prognosis

Lung transplant recipients experience a particularly high incidence of Aspergillus infection in comparison with other solid-organ transplantations. This study was conducted to determine the incidence of Aspergillus colonisation and invasive aspergillosis, and the impact on long-term survival associated with Aspergillus infection. A retrospective study of 362 consecutive lung transplant patients from a single national centre who were transplanted 1992–2003 were studied. Twenty-seven patients were excluded due to incomplete or missing files. A total of 105/335 (31%) patients had evidence of Aspergillus infection (colonisation or invasion), including 83 (25%) patients with colonisation and 22 (6%) patients with radiographic or histological evidence of invasive disease. Most of the infections occurred within the first 3 months after transplantation. Cystic fibrosis (CF) patients had higher incidences of colonisation and invasive disease [15 (42%) and 4 (11%) of 36 patients] than non-CF patients [68 (23%) and 18 (6%) of 299 patients] (P = 0.01). Invasive aspergillosis was associated with 58% mortality after 2 years, whereas colonisation was not associated with early increased mortality but was associated with increased mortality after 5 years compared to non-infected patients (P < 0.05). An analysis of demographic factors showed that donor age [OR 1.40 per decade (95% CI 1.10-1.80)], ischaemia time [OR 1.17 per hour increase (95% CI 1.01–1.39)], and use of daclizumab versus polyclonal induction [OR 2.05 (95% CI 1.14–3.75)] were independent risk factors for Aspergillus infection. Invasive aspergillosis was associated with early and high mortality in lung transplant patients. Colonisation with Aspergillus was also associated with a significant increase in mortality after 5 years. CF patients have a higher incidence of Aspergillus infection than non-CF patients.