Necropsy findings of koalas from the Mount Lofty Ranges population in South Australia.

OBJECTIVE: This study reports necropsy findings of koalas from the Mount Lofty Ranges region in order to identify health threats to this mainland South Australian population. METHODS: Koalas from the Mount Lofty Ranges region (n = 85) that had died or been euthanased on welfare grounds were examined at necropsy during 2012-13 at the School of Animal and Veterinary Sciences, University of Adelaide. Disease findings, approximate age, sex and body condition of koalas were recorded. Histopathological examination was undertaken on gross lesions and in suspect cases, skin scrapings taken for microscopy and PCR performed for Chlamydia pecorum detection. RESULTS: Traumatic injury was the most common necropsy finding (48/85; 57%), caused by motor vehicle accidents (35/48; 73%), canine attacks (11/48; 23%) or bushfire burns (2/48; 4%). Oxalate nephrosis (27/85; 32%) was also more common than other conditions. Infectious diseases included chlamydiosis (10/85; 12%) and sarcoptic mange (7/85; 8%). Marked testis asymmetry was evident in 11% (6/56) of males, with histopathology suggestive of atrophic change in four animals. Other pathological conditions included gastrointestinal disease (7/85; 8%) and respiratory disease (3/85; 4%). Almost half of the koalas (38/85; 45%) were found to have two or more abnormalities at necropsy. CONCLUSION: This study found trauma, mainly from motor vehicle accidents, and oxalate nephrosis to be the predominant causes of death and/or disease in koalas from the Mount Lofty Ranges region. Recent emergence of both clinical chlamydiosis and sarcoptic mange has also occurred, providing insight into the health status and causes of disease or injury in this South Australian mainland koala population.

Acute risk change (ARC) identifies outlier institutions in perioperative cardiac surgical care when the standardized mortality ratio cannot.

BACKGROUND: With improvements in short-term mortality after cardiac surgery, the sensitivity of the standardized mortality ratio (SMR) as a performance-monitoring tool has declined. We assessed acute risk change (ARC) as a new and potentially more sensitive metric to differentiate overall cardiac surgical unit performance. METHODS: Retrospective analysis of the Australian and New Zealand Society of Cardiac and Thoracic Surgeons database and Australian and New Zealand Intensive Care Society Adult Patient Database was performed. The 16 656 patients who underwent coronary artery bypass grafting or cardiac valve procedures during a 4 yr period were included. The ARC was generated using the change between preoperative and postoperative probability of death. Outlier institutions were those with higher (outside 99.8% confidence intervals) ARC or SMR on annual and 4 yr funnel plots. Outliers were grouped and compared with non-outliers for baseline characteristics, intraoperative events, and postoperative morbidity. RESULTS: No outliers were identified using SMR. Two outliers were identified using ARC. Outliers had higher rates of new renal failure (5.7 vs 4.5%, P=0.017), stroke (1.6 vs 0.9%, P=0.001), reoperation (9 vs 6.0%, P<0.001), and prolonged ventilation (15.3 vs 9.5%, P<0.001). Outliers transfused more blood products (P<0.001) and had longer cardiopulmonary bypass times (P<0.001) and less senior surgeons operating (P<0.001). CONCLUSIONS: Acute risk change was able to discriminate between units where SMR could not. Outliers had more adverse events. Acute risk change can be calculated before mortality outcome and identifies outliers with lower patient numbers. This may allow early recognition and investigation of outlier units.

The tumor microenvironment in esophageal cancer.

Esophageal cancer is a deadly disease, ranking sixth among all cancers in mortality. Despite incremental advances in diagnostics and therapeutics, esophageal cancer still carries a poor prognosis, and thus, there remains a need to elucidate the molecular mechanisms underlying this disease. There is accumulating evidence that a comprehensive understanding of the molecular composition of esophageal cancer requires attention to not only tumor cells but also the tumor microenvironment (TME), which contains diverse cell populations, signaling factors and structural molecules that interact with tumor cells and support all stages of tumorigenesis. In esophageal cancer, environmental exposures can trigger chronic inflammation, which leads to constitutive activation of pro-inflammatory signaling pathways that promote survival and proliferation. Antitumor immunity is attenuated by cell populations such as myeloid-derived suppressor cells and regulatory T cells, as well as immune checkpoints like programmed death-1. Other immune cells such as tumor-associated macrophages can have other pro-tumorigenic functions, including the induction of angiogenesis and tumor cell invasion. Cancer-associated fibroblasts secrete growth factors and alter the extracellular matrix to create a tumor niche and enhance tumor cell migration and metastasis. Further study of how these TME components relate to the different stages of tumor progression in each esophageal cancer subtype will lead to development of novel and specific TME-targeting therapeutic strategies, which offer considerable potential especially in the setting of combination therapy.

Findings of the first ANZICS conference on the role of intensive care in Rapid Response Teams.

Rapid Response Teams (RRTs) are specialised teams introduced into hospitals to improve the outcomes of deteriorating ward patients. Although Rapid Response Systems (RRSs) were developed by the intensive care unit (ICU) community, there is variability in their delivery, and consultant involvement, supervision and leadership appears to be relatively infrequent. In July 2014, the Australian and New Zealand Intensive Care Society (ANZICS) convened the first conference on the role of intensive care medicine in RRTs in Australia and New Zealand. The conference explored RRSs in the broader role of patient safety, resourcing and staffing of RRTs, effect on ICU workload, different RRT models, the outcomes of RRT patients and original research projects in the area of RRSs. Issues around education and training of both ICU registrars and nurses were examined, and the role of team training explored. Measures to assess the effectiveness of the RRS and RRT at the level of health system and hospital, team performance and team effectiveness were discussed, and the need to develop a bi-national ANZICS RRT patient database was presented. Strategies to prevent patient deterioration in the 'pre-RRT' period were discussed, including education of ward nurses and doctors, as well as an overarching governance structure. The role of the ICU in deteriorating ward patients was debated and an integrated model of acute care presented. This article summarises the findings of the conference and presents recommendations on the role of intensive care medicine in RRTs in Australia and New Zealand.

Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure.

Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors were associated with shorter renal allograft survival in a prior single-center report. APOL1 G1 and G2 variants were genotyped in newly accrued DNA samples from African American deceased donors of kidneys recovered and/or transplanted in Alabama and North Carolina. APOL1 genotypes and allograft outcomes in subsequent transplants from 55 U.S. centers were linked, adjusting for age, sex and race/ethnicity of recipients, HLA match, cold ischemia time, panel reactive antibody levels, and donor type. For 221 transplantations from kidneys recovered in Alabama, there was a statistical trend toward shorter allograft survival in recipients of two-APOL1-nephropathy-variant kidneys (hazard ratio [HR] 2.71; p = 0.06). For all 675 kidneys transplanted from donors at both centers, APOL1 genotype (HR 2.26; p = 0.001) and African American recipient race/ethnicity (HR 1.60; p = 0.03) were associated with allograft failure. Kidneys from African American deceased donors with two APOL1 nephropathy variants reproducibly associate with higher risk for allograft failure after transplantation. These findings warrant consideration of rapidly genotyping deceased African American kidney donors for APOL1 risk variants at organ recovery and incorporation of results into allocation and informed-consent processes.

Trends in the incidence of intensive care unit invasive mechanical ventilation and subsequent 2-year survival in very elderly New Zealanders.

BACKGROUND: The number of elderly in the general population is growing. There are therefore implications for the provision of intensive care unit (ICU) care to elderly patients. AIM: Our aim was to determine the incidence of ICU invasive mechanical ventilation (IMV), long-term outcomes of patients treated with IMV, and trends in these variables over a 10-year period in New Zealand, with a focus on very elderly patients (aged 80 years and over). METHODS: Analysis of New Zealand public hospital discharge data from July 1999 to June 2010, with linked long-term mortality data. Transfers or readmissions to different hospitals were linked using a national unique patient identifier. RESULTS: There were 58 003 patients treated with IMV in a New Zealand ICU. Of these patients, 6.6% were very elderly. Population rates of ICU IMV declined or were static over all age groups. The 2-year mortality rate ranged from 15% in patients aged 16-39 years to 52% in the very elderly. The 2-year mortality rates for the very elderly were highest for acute medical patients (78%), followed by acute surgical admissions (46%) and elective admissions (35%). The 2-year mortality rate for all patients declined over the study period, and declined or was static for all age groups and admission types. In the very elderly, the standardised mortality ratio of patients surviving at 1 year who survived their second year after admission, compared with the age-matched general population, was lower than all other age groups. CONCLUSION: For very elderly patients over the period 1999-2009, the population rate of IMV was static and 2-year mortality declined.

Social spaces for young children in hospital.

BACKGROUND: In the last number of years heightened interest has been attributed to the impact of hospital environments on children's psychosocial well-being. With policy largely built around adult assumptions, knowledge about what constitutes a child-friendly hospital environment from young children's perspectives has been lacking. If hospital environments are to aspire to being child friendly then the views of younger aged children must be taken into account. The current study investigated young children's perspectives of hospital social spaces to inform the design of the built environment of a new children's hospital. METHODS: An exploratory qualitative participatory design was employed. Data were collected through semi-structured interviews (one-to-one and group workshops) which incorporated art-based activities to actively engage young children. Fifty-five young children aged 5 to 8 years with various acute and chronic illnesses were recruited from inpatient, outpatient and emergency departments of three children's hospitals. RESULTS: Young children want a diversity of readily available, independently accessible, age, gender and developmentally appropriate leisure and entertainment facilities seamlessly integrated throughout the hospital environment. Such activities were invaluable for creating a positive hospital experience for children by combating boredom, enriching choice and control and reducing a sense of isolation through enhanced socialization. When in hospital, young children want to feel socially connected to the internal hospital community as well as to the outside world. Technology can assist to broaden the spectrum of children's social connectivity when in hospital - to home, school and the wider outside world. CONCLUSION: While technology offers many opportunities to support children's psychosocial well-being when in confined healthcare spaces, the implementation and operation of such services and systems require much further research in the areas of ethics, facilitation, organizational impact and evaluation.

Relationship of opioid prescription sales and overdoses, North Carolina.

BACKGROUND: In the United States, fatal drug overdoses have tripled since 1991. This escalation in deaths is believed to be driven primarily by prescription opioid medications. This investigation compared trends and patterns in sales of opioids, opioid drug overdoses treated in emergency departments (EDs), and unintentional overdose deaths in North Carolina (NC). METHODS: Our ecological study compared rates of opioid sales, opioid related ED overdoses, and unintentional drug overdose deaths in NC. Annual sales data, provided by the Drug Enforcement Administration, for select opioids were converted into morphine equivalents and aggregated by zip code. These opioid drug sales rates were trended from 1997 to 2010. In addition, opioid sales were correlated and compared to opioid related ED visits, which came from a Centers for Disease Control and Prevention syndromic surveillance system, and unintentional overdose deaths, which came from NC Vital Statistics, from 2008 to 2010. Finally, spatial cluster analysis was performed and rates were mapped by zip code in 2010. RESULTS: Opioid sales increased substantially from 1997 to 2010. From 2008 to 2010, the quarterly rates of opioid drug overdoses treated in EDs and opioid sales correlated (r=0.68, p=0.02). Specific regions of the state, particularly in the southern and western corners, had both high rates of prescription opioid sales and overdoses. CONCLUSIONS: Temporal trends in sales of prescription opioids correlate with trends in opioid related ED visits. The spatial correlation of opioid sales with ED visit rates shows that opioid sales data may be a timely way to identify high-risk communities in the absence of timely ED data.

Implication of European-derived adiposity loci in African Americans.

OBJECTIVE: Recent genome-wide association studies (GWAS) have identified multiple novel loci associated with adiposity in European-derived study populations. Limited study of these loci has been reported in African Americans. Here we examined the effects of these previously identified adiposity loci in African Americans. METHODS: A total of 46 representative single-nucleotide polymorphisms (SNPs) in 19 loci that were previously reported in GWAS in Europeans (including FTO and MC4R) were genotyped in 4992 subjects from six African-American cohorts. These SNPs were tested for association with body mass index (BMI) after adjustment for age, gender, disease status and population structure in each cohort. Meta-analysis was conducted to combine the results. RESULTS: Meta-analysis of 4992 subjects revealed seven SNPs near four loci, including NEGR1, TMEM18, SH2B1 /ATP2A1 and MC4R, showing significant association at 0.005

The APOL1 gene and allograft survival after kidney transplantation.

Coding variants in the apolipoprotein L1 gene (APOL1) are strongly associated with nephropathy in African Americans (AAs). The effect of transplanting kidneys from AA donors with two APOL1 nephropathy risk variants is unknown. APOL1 risk variants were genotyped in 106 AA deceased organ donors and graft survival assessed in 136 resultant kidney transplants. Cox-proportional hazard models tested for association between time to graft failure and donor APOL1 genotypes. The mean follow-up was 26.4 ± 21.8 months. Twenty-two of 136 transplanted kidneys (16%) were from donors with two APOL1 nephropathy risk variants. Twenty-five grafts failed; eight (32%) had two APOL1 risk variants. A multivariate model accounting for donor APOL1 genotype, overall African ancestry, expanded criteria donation, recipient age and gender, HLA mismatch, CIT and PRA revealed that graft survival was significantly shorter in donor kidneys with two APOL1 risk variants (hazard ratio [HR] 3.84; p = 0.008) and higher HLA mismatch (HR 1.52; p = 0.03), but not for overall African ancestry excluding APOL1. Kidneys from AA deceased donors harboring two APOL1 risk variants failed more rapidly after renal transplantation than those with zero or one risk variants. If replicated, APOL1 genotyping could improve the donor selection process and maximize long-term renal allograft survival.

Incidence of and risk factors for bacteraemia in HIV-infected adults in the era of highly active antiretroviral therapy.

BACKGROUND: HIV-infected patients have an increased risk for bacteraemia compared with HIV-negative patients. Few data exist on the incidence of and risk factors for bacteraemia across time in the current era of highly active antiretroviral therapy (HAART). METHODS: We assessed the incidence of bacteraemia among patients followed between 2000 and 2008 at 10 HIV Research Network sites. This large multisite, multistate clinical cohort study collected demographic, clinical and therapeutic data longitudinally. International Statistical Classification of Diseases and Related Health Problems (ICD)-9 codes were examined to identify all cases of in-patient bacteraemia. Logistic regression analysis was used to assess risk factors for bacteraemia and trends over time in the odds of bacteraemia. RESULTS: A total of 39 318 patients were followed for 146 289 person-years (PY). During the study period, there were 2025 episodes of bacteraemia (incidence 13.8 events/1000 PY). The most common bacteraemia diagnosis was 'bacteraemia, not otherwise specified (NOS)' (51%) followed by Staphylococcus aureus (16%) and Streptococcus species (6.5%). In multivariate analysis, the likelihood of bacteraemia was found to have increased in 2005-2008, compared with 2000. Other factors associated with higher odds of bacteraemia included a history of injection drug use (IDU), age ≥ 50 years, Black race and greater immunosuppression. CONCLUSIONS: The likelihood of bacteraemia has risen slightly in recent years. Patients who are Black or have a history of IDU are at higher risk. Further research is needed to identify reasons for this increase and to evaluate programmes designed to reduce the bacteraemia risk.

A unique snapshot of intensive care resources in Australia and New Zealand.

The objective of this study was to analyse and report on the distribution and attributes of intensive care services in Australia and New Zealand for the 2005/2006 financial year A survey was mailed to 155 Australian and 26 New Zealand intensive care units (ICU) listed on the database of the Australian and New Zealand Intensive Care Society. A descriptive analytical approach was used. Of the 181 ICUs, 177 provided data. In Australia there were 100 public sector and 51 private sector ICUs and in New Zealand, 24 public sector and two private sector ICUs. These units contain 1485 available beds in the public sector and 538 available beds in the private sector Calculations to determine beds per 100,000 population, medical specialists per 1000 patient days and registered nurses per 1000 patient days showed wide variation. International comparisons are limited by lack of data; however it does appear that intensive care patients in Australia and New Zealand have very good outcomes.

Comparison of HTN management in patients with diabetes between rural and urban primary care clinics in Northeastern Colorado - a report from SNOCAP.

INTRODUCTION: In the USA, rural residents have a higher burden of disease and more limited access to care than urban residents. There are conflicting data on quality of care in rural settings. To evaluate this relationship, blood pressure (BP) control and decision-making at the point of care in patients with diabetes were examined for rural and urban medical providers in Northeastern Colorado. METHODS: Twenty-six primary care practices in two practice-based research networks in Colorado participated: 13 in rural settings and 13 urban. Questionnaires were completed after each encounter with an adult with type 2 diabetes. The survey obtained: (1) demographic information; (2) BP result; (3) whether action was taken; (4) if action was taken, type of action; and (5) if no action, what reasons were given for this inaction. Bivariate and multivariate analyses were performed to identify predictors of action. RESULTS: In total, 778 surveys were completed. Mean BP was 130/74 (+/-18.8/12.0) with BP in rural residents being slightly lower than for urban residents. Rural residents were more likely to be non-Hispanic white, on Medicare, on multiple medications, and less likely to be on Medicaid. Sixty-five percent of urban patients exceeded BP goals, as did 58% of rural patients. Action rates for those with elevated BP in rural areas were not significantly different than those in urban areas (OR 0.75 [0.45-1.25] p = 0.27). The reasons for inaction were similar. CONCLUSION: In this study of patients with diabetes, quality of care for elevated BP was similar in rural and urban areas.

Variants in intron 13 of the ELMO1 gene are associated with diabetic nephropathy in African Americans.

Variants in the engulfment and cell motility 1 (ELMO1) gene are associated with nephropathy due to type 2 diabetes mellitus (T2DM) in a Japanese cohort. We comprehensively evaluated this gene in African American (AA) T2DM patients with end-stage renal disease (ESRD). Three hundred and nine HapMap tagging SNPs and 9 reportedly associated SNPs were genotyped in 577 AA T2DM-ESRD patients and 596 AA non-diabetic controls, plus 43 non-diabetic European American controls and 45 Yoruba Nigerian samples for admixture adjustment. Replication analyses were conducted in 558 AA with T2DM-ESRD and 564 controls without diabetes. Extension analyses included 328 AA with T2DM lacking nephropathy and 326 with non-diabetic ESRD. The original and replication analyses confirmed association with four SNPs in intron 13 (permutation p-values for combined analyses = 0.001-0.003), one in intron 1 (P = 0.004) and one in intron 5 (P = 0.002) with T2DM-associated ESRD. In a subsequent combined analysis of all 1,135 T2DM-ESRD cases and 1,160 controls, an additional 7 intron 13 SNPs produced evidence of association (P = 3.5 x 10(-5)- P = 0.05). No associations were seen with these SNPs in those with T2DM lacking nephropathy or with ESRD due to non-diabetic causes. Variants in intron 13 of the ELMO1 gene appear to confer risk for diabetic nephropathy in AA.

Genome-wide linkage scans for renal function and albuminuria in Type 2 diabetes mellitus: the Diabetes Heart Study.

AIMS/HYPOTHESIS: Glomerular filtration rate (GFR), end-stage renal disease and albuminuria are highly heritable. We performed a genome-wide linkage scan in 416 Diabetes Heart Study (DHS) families to detect loci that contributed to renal function and albuminuria. MATERIALS AND METHODS: A total of 1067 individuals (900 with Type 2 diabetes mellitus) from 348 European American and 68 African American DHS families had measures of urine albumin : creatinine ratio (ACR), serum creatinine concentration and Modification of Diet in Renal Disease estimated GFR (eGFR). Variance components quantitative trait linkage analysis (using SOLAR) was computed. RESULTS: Participants had mean +/- sd age 61.4 +/- 9.4 years; diabetes duration 10.5 +/- 7.4 years; eGFR 1.15 +/- 0.32 ml/sec; and urine ACR 15.8 +/- 67.2 mmol/l (median 1.4). In all families, significant evidence for linkage of GFR was observed on chromosome 2p16 (log of the odds; LOD = 4.31 at 72.0 cM, ATA47C04P/D2S1352) and 1p36 (LOD = 3.81 at 45.0 cM, D1S3669/D1S3720), with suggestive evidence on 7q21 (LOD = 2.42 at 99.0 cM, D7S820/D7S821) and 13q13 (LOD = 2.28 at 28.0 cM, D13S1493/D13S894). The evidence for linkage to ACR was far weaker, on 13q21-q22 (LOD = 1.84 at 50 cM, D13S1807/D13S800), 3p24-p23 (LOD = 1.81 at 58 cM, D3S3038/D3S2432) and 10p11 (LOD = 1.78 at 71.0 cM, D10S1208/D10S1221). CONCLUSIONS/INTERPRETATIONS: The eGFR linkage peaks on 2p16, 7q21 and 13q13 closely overlap with nephropathy peaks identified in family studies enriched for severe kidney disease. These diabetes-enriched families provide an opportunity to map genes regulating renal function, potentially leading to the identification of genes producing nephropathy susceptibility in subjects with Type 2 diabetes.

The impact of illicit drug use and substance abuse treatment on adherence to HAART.

High levels of adherence to highly active antiretroviral therapy (HAART) are essential for virologic suppression and longer survival in patients with HIV. We examined the effects of substance abuse treatment, current versus former substance use, and hazardous/binge drinking on adherence to HAART. During 2003, 659 HIV patients on HAART in primary care were interviewed. Adherence was defined as > or =95% adherence to all antiretroviral medications. Current substance users used illicit drugs and/or hazardous/binge drinking within the past six months, while former users had not used substances for at least six months. Logistic regression analyses of adherence to HAART included demographic, clinical and substance abuse variables. Sixty-seven percent of the sample reported 95% adherence or greater. However, current users (60%) were significantly less likely to be adherent than former (68%) or never users (77%). In multivariate analysis, former users in substance abuse treatment were as adherent to HAART as never users (Adjusted Odds Ratio (AOR)=0.82; p>0.5). In contrast, former users who had not received recent substance abuse treatment were significantly less adherent than never users (AOR=0.61; p=0.05). Current substance users were significantly less adherent than never users, regardless of substance abuse treatment (p<0.01). Substance abuse treatment interacts with current versus former drug use status to affect adherence to HAART. Substance abuse treatment may improve HAART adherence for former substance users.

Loci contributing to adult height and body mass index in African American families ascertained for type 2 diabetes.

Height and body mass index (BMI) have high heritability in most studies. High BMI and reduced height are well-recognized as important risk factors for a number of cardiovascular diseases. We investigated these phenotypes in African American families originally ascertained for studies of linkage with type 2 diabetes using self-reported height and weight. We conducted a genome wide scan in 221 families containing 580 individuals and 672 relative pairs of African American descent. Estimates of heritability and support for linkage were assessed by genetic variance component analyses using SOLAR software. The estimated heritabilities for height and BMI were 0.43 and 0.64, respectively. We have identified major loci contributing to variation in height on chromosomes 15 (LOD = 2.61 at 35 cM, p = 0.0004), 3 (LOD = 1.82 at 84 cM, p = 0.0029), 8 (LOD = 1.92 at 135 cM, p = 0.0024) and 17 (LOD = 1.70 at 110 cM, p = 0.0044). A broad region on chromosome 4 supported evidence of linkage to variation in BMI, with the highest LOD = 2.66 at 168 cM (p = 0.0005). Two height loci and two BMI loci appear to confirm the existence of quantitative trait loci previously identified by other studies, providing important replicative data to allow further resolution of linkage regions suitable for positional cloning of these cardiovascular disease risk loci.

Global distribution and outcomes for Candida species causing invasive candidiasis: results from an international randomized double-blind study of caspofungin versus amphotericin B for the treatment of invasive candidiasis.

In a randomized study, caspofungin was compared with amphotericin B for the treatment of invasive candidiasis in a total of 239 adults from 56 sites in 20 countries. This study provided a unique opportunity to assess the frequency and outcome of invasive candidiasis caused by different Candida species worldwide, and the results are presented here. Efficacy was primarily assessed at the end of intravenous therapy using a modified intent-to-treat (MITT) analysis. This analysis was performed on 224 of the 239 patients enrolled in the study. Attempts were made to collect baseline Candida isolates from all patients for species identification at a central laboratory. Yeasts were identified to the species level using two commercial systems and microscopic examination. Viable baseline isolates were recovered from 210 of the 224 (94%) patients included in the MITT analysis. Candida albicans was the most frequently isolated species in all regions and was responsible for 45% of cases overall. Nevertheless, the majority of cases of infection were caused by non- albicans Candida species. In the USA and Canada, Candida glabrata was the second most commonly isolated pathogen (18%). In contrast, Candida parapsilosis and Candida tropicalis accounted for 55% of cases in Latin America. Outcomes were comparable for patients treated with caspofungin (74% overall; 64% and 80% for infections due to Candida albicans and non- albicans species) and amphotericin B (62% overall; 58% and 68% for infections due to Candida albicans and non- albicans species), and were generally similar across continents. The distribution of Candida species isolated from patients enrolled in a clinical trial may not be representative of pathogens causing invasive candidiasis in the general population. Nevertheless, our findings may affect the regional choice of empirical antifungal therapy for seriously ill patients with suspected or documented invasive candidiasis since different Candida species have varying susceptibility to conventional antifungal drugs.

Comparative in vitro activity of ertapenem against bacterial pathogens isolated from patients with lower respiratory tract infections.

This study compared the in vitro activity of ertapenem, ceftriaxone, cefepime, ciprofloxacin and amoxicillin-clavulanate against 381 aerobic and facultative bacterial pathogens isolated from 320 patients with acute bacterial exacerbation of chronic bronchitis or community-acquired pneumonia. Streptococcus pneumoniae and Haemophilus influenzae accounted for 54.6% of the isolates. The ertapenem MIC was < or =2 mg/L for 98.4% of isolates and > or =8 mg/L for 1.0% (all methicillin-resistant Staphylococcus aureus). Ertapenem had the most potent activity against Enterobacteriaceae, Moraxella catarrhalis, and methicillin-susceptible S. aureus, and its activity against H. influenzae and H. parainfluenzae, all strains of which were susceptible, was not altered by beta-lactamase production. Only one S. pneumoniae strain, a penicillin-resistant isolate, was resistant to ertapenem. Ertapenem was highly active in vitro against pyogenic bacteria recovered from patients with community-acquired lower respiratory tract infections.