Genomic dissection of Klebsiella pneumoniae infections in hospital patients reveals insights into an opportunistic pathogen.

Klebsiella pneumoniae is a major cause of opportunistic healthcare-associated infections, which are increasingly complicated by the presence of extended-spectrum beta-lactamases (ESBLs) and carbapenem resistance. We conducted a year-long prospective surveillance study of K. pneumoniae clinical isolates in hospital patients. Whole-genome sequence (WGS) data reveals a diverse pathogen population, including other species within the K. pneumoniae species complex (18%). Several infections were caused by K. variicola/K. pneumoniae hybrids, one of which shows evidence of nosocomial transmission. A wide range of antimicrobial resistance (AMR) phenotypes are observed, and diverse genetic mechanisms identified (mainly plasmid-borne genes). ESBLs are correlated with presence of other acquired AMR genes (median n = 10). Bacterial genomic features associated with nosocomial onset are ESBLs (OR 2.34, p = 0.015) and rhamnose-positive capsules (OR 3.12, p < 0.001). Virulence plasmid-encoded features (aerobactin, hypermucoidy) are observed at low-prevalence (<3%), mostly in community-onset cases. WGS-confirmed nosocomial transmission is implicated in just 10% of cases, but strongly associated with ESBLs (OR 21, p < 1 × 10-11). We estimate 28% risk of onward nosocomial transmission for ESBL-positive strains vs 1.7% for ESBL-negative strains. These data indicate that K. pneumoniae infections in hospitalised patients are due largely to opportunistic infections with diverse strains, with an additional burden from nosocomially-transmitted AMR strains and community-acquired hypervirulent strains.

Genomic surveillance of antimicrobial resistant bacterial colonisation and infection in intensive care patients.

BACKGROUND: Third-generation cephalosporin-resistant Gram-negatives (3GCR-GN) and vancomycin-resistant enterococci (VRE) are common causes of multi-drug resistant healthcare-associated infections, for which gut colonisation is considered a prerequisite. However, there remains a key knowledge gap about colonisation and infection dynamics in high-risk settings such as the intensive care unit (ICU), thus hampering infection prevention efforts. METHODS: We performed a three-month prospective genomic survey of infecting and gut-colonising 3GCR-GN and VRE among patients admitted to an Australian ICU. Bacteria were isolated from rectal swabs (n = 287 and n = 103 patients ≤2 and > 2 days from admission, respectively) and diagnostic clinical specimens between Dec 2013 and March 2014. Isolates were subjected to Illumina whole-genome sequencing (n = 127 3GCR-GN, n = 41 VRE). Multi-locus sequence types (STs) and antimicrobial resistance determinants were identified from de novo assemblies. Twenty-three isolates were selected for sequencing on the Oxford Nanopore MinION device to generate completed reference genomes (one for each ST isolated from ≥2 patients). Single nucleotide variants (SNVs) were identified by read mapping and variant calling against these references. RESULTS: Among 287 patients screened on admission, 17.4 and 8.4% were colonised by 3GCR-GN and VRE, respectively. Escherichia coli was the most common species (n = 36 episodes, 58.1%) and the most common cause of 3GCR-GN infection. Only two VRE infections were identified. The rate of infection among patients colonised with E. coli was low, but higher than those who were not colonised on admission (n = 2/33, 6% vs n = 4/254, 2%, respectively, p = 0.3). While few patients were colonised with 3GCR- Klebsiella pneumoniae or Pseudomonas aeruginosa on admission (n = 4), all such patients developed infections with the colonising strain. Genomic analyses revealed 10 putative nosocomial transmission clusters (≤20 SNVs for 3GCR-GN, ≤3 SNVs for VRE): four VRE, six 3GCR-GN, with epidemiologically linked clusters accounting for 21 and 6% of episodes, respectively (OR 4.3, p = 0.02). CONCLUSIONS: 3GCR-E. coli and VRE were the most common gut colonisers. E. coli was the most common cause of 3GCR-GN infection, but other 3GCR-GN species showed greater risk for infection in colonised patients. Larger studies are warranted to elucidate the relative risks of different colonisers and guide the use of screening in ICU infection control.

Antimicrobial-Resistant Klebsiella pneumoniae Carriage and Infection in Specialized Geriatric Care Wards Linked to Acquisition in the Referring Hospital.

Background: Klebsiella pneumoniae is a leading cause of extended-spectrum ß-lactamase (ESBL)-producing hospital-associated infections, for which elderly patients are at increased risk. Methods: We conducted a 1-year prospective cohort study, in which a third of patients admitted to 2 geriatric wards in a specialized hospital were recruited and screened for carriage of K. pneumoniae by microbiological culture. Clinical isolates were monitored via the hospital laboratory. Colonizing and clinical isolates were subjected to whole-genome sequencing and antimicrobial susceptibility testing. Results: K. pneumoniae throat carriage prevalence was 4.1%, rectal carriage 10.8%, and ESBL carriage 1.7%, and the incidence of K. pneumoniae infection was 1.2%. The isolates were diverse, and most patients were colonized or infected with a unique phylogenetic lineage, with no evidence of transmission in the wards. ESBL strains carried blaCTX-M-15 and belonged to clones associated with hospital-acquired ESBL infections in other countries (sequence type [ST] 29, ST323, and ST340). One also carried the carbapenemase blaIMP-26. Genomic and epidemiological data provided evidence that ESBL strains were acquired in the referring hospital. Nanopore sequencing also identified strain-to-strain transmission of a blaCTX-M-15 FIBK/FIIK plasmid in the referring hospital. Conclusions: The data suggest the major source of K. pneumoniae was the patient's own gut microbiome, but ESBL strains were acquired in the referring hospital. This highlights the importance of the wider hospital network to understanding K. pneumoniae risk and infection prevention. Rectal screening for ESBL organisms on admission to geriatric wards could help inform patient management and infection control in such facilities.

Outcomes following detection of low level plasma HIV RNA in HIV-infected patients previously virologically suppressed on antiretroviral therapy: a retrospective observational study.

BACKGROUND: Progressively sensitive assays for plasma HIV RNA have led to increased detection of plasma HIV RNA between 20 and 200 copies/ml, known as low level viremia (LLV) when recurrent or persistent, in HIV-infected patients on antiretroviral therapy (ART). The aim of this study was to determine outcomes following initial detection of LLV in an Australian cohort. METHODS: A retrospective study using the HIV Service Database (Alfred Hospital) included all patients on ART who recorded plasma HIV RNA 20-200 copies/mL following prior virological suppression (viral load (VL) HIV RNA <20 copies/mL) over 2 years (2010 to 2012), with follow-up to June 2013. Factors associated with subsequent virological outcome were assessed via univariate and multivariate analysis. RESULTS: Of 919 patients managed by The Alfred HIV service, 207 (22.5%) met inclusion criteria. Mean age was 48.8 years, 91.3% were male. During follow-up, 54% patients recorded no further HIV RNA 20-200 copies/mL (viral blip); 39% had recurrent or persistent VL 20-200 copies/mL (LLV); and 7% progressed to virological failure with VL >200 copies/mL. Factors associated with LLV included co-morbid type 2 diabetes, shorter prior virological suppression and lower nadir CD4 cell count. Clinician management of VL 20-200 copies/mL was generally conservative, with infrequent requests for genotypic analysis (3.3% cases) or change in ART (<1% cases). CONCLUSIONS: LLV following virological suppression is common, and occurred as an isolated viral blip in half the patients. Those patients with persistent or recurrent LLV had higher rates of type 2 diabetes, shorter prior virological suppression and lower nadir CD4 cell count.

Comparing non-occupational post-exposure prophylaxis drug regimens for HIV: insights from a linked HIV surveillance system.

Background International non-occupational post-exposure prophylaxis (NPEP) guidelines recommend routine use of three drug NPEP regimens, despite absence of evidence for greater prevention efficacy compared with two drug regimens. This study examines the potential for excess HIV seroconversions among high-risk men who have sex with men (MSM) reporting receptive anal intercourse with a source of unknown HIV serostatus (RAIU) following a two-drug versus a three-drug NPEP regimen. METHODS: Data for MSM in the Victorian NPEP service database between 10 August 2005 and 31 December 2012 were linked with all Victorian HIV notifications up to 31 December 2013. The primary outcome was NPEP failure following NPEP presentation among MSM reporting RAIU, stratified by the number of drugs prescribed. RESULTS: Among 1482 MSM reporting 2002 episodes of RAIU and prescribed two- or three-drug NPEP, 70 seroconverted to HIV, but only 19 were considered possible NPEP failures. HIV diagnosis incidence among men reporting RAIU was 1.2/100 person years (PY) (95%CI=1.0-1.6); 1.1/100 PY (95%CI=0.8-1.4) among MSM prescribed two drugs and 2.2/100 PY (95%CI=1.4-3.7) among MSM prescribed three drugs (P<0.01). Of the 19 possible NPEP failures, 13 (0.7%) were prescribed two drugs and six (2.7%) three drugs (P<0.001). CONCLUSIONS: This study suggests that two-drug NPEP regimens do not result in excess seroconversions compared with three-drug regimens when used following RAIU. Clinical services should carefully consider their use of three drug NPEP and whether resources might be better invested in other prevention strategies, particularly pre-exposure prophylaxis (PrEP).

An effective strategy for influenza vaccination of healthcare workers in Australia: experience at a large health service without a mandatory policy.

BACKGROUND: Annual influenza vaccination of healthcare workers (HCWs) is recommended in Australia, but uptake in healthcare facilities has historically been low (approximately 50%). The objective of this study was to develop and implement a dedicated campaign to improve uptake of staff influenza annual vaccination at a large Australian health service. METHODS: A quality improvement program was developed at Alfred Health, a tertiary metropolitan health service spanning 3 campuses. Pre-campaign evaluation was performed by questionnaire in 2013 to plan a multimodal vaccination strategy. Reasons for and against vaccination were captured. A campaign targeting clinical and non-clinical healthcare workers was then implemented between March 31 and July 31 2014. Proportional uptake of influenza vaccination was determined by campus and staff category. RESULTS: Pre-campaign questionnaire responses were received from 1328/6879 HCWs (response rate 20.4%), of which 76% were vaccinated. Common beliefs held by unvaccinated staff included vaccine ineffectiveness (37.1%), that vaccination makes staff unwell (21.0%), or that vaccination is not required because staff are at low risk for acquiring influenza (20.2%). In 2014, 6009/7480 (80.3%) staff were vaccinated, with significant improvement in uptake across all campuses and amongst nursing, medical and allied health staff categories from 2013 to 2014 (p < 0.0001). CONCLUSIONS: A non-mandatory multimodal strategy utilising social marketing and a customised staff database was successful in increasing influenza vaccination uptake by all staff categories. The sustainability of dedicated campaigns must be evaluated.

HIV treatment outcomes among people who inject drugs in Victoria, Australia.

BACKGROUND: People who inject drugs (PWID) are a key population affected by HIV. We assessed the effectiveness of HIV treatment among a clinical cohort of people living with HIV (PLHIV) diagnosed and referred for community-based antiretroviral therapy (ART) in Victoria, Australia. METHODS: HIV notification data from a central statewide registry were matched with HIV clinical data from two large HIV treatment centers in Melbourne. We used survival analysis and Cox proportional hazard models to estimate time to AIDS and death for PWID in HIV treatment, compared with non-injectors, in the period 1996-2008. RESULTS: Of the 871 individuals, 93 (10.8%) had injecting as an exposure category and 671 (86%) had ever commenced ART. Adjusted analysis showed younger age, high initial CD4 cell count (>500 cells/mm(3)) or ever having a CD4 cell count >500/mm(3), and more recent calendar year of ART commencement were all associated with reduced hazards for AIDS and death, while older age, low initial CD4 cell count (<200/mm(3)), ever having a CD4 count <200/mm(3) (before or during treatment) and high initial viral load (>5 log10) were associated with increased risk of AIDS and death. PWID were no more likely to experience AIDS (HR 0.98 [0.54-1.80]) or death (HR 0.78 [0.18-3.42]) than non-injectors. CONCLUSION: Survival of HIV-infected PWID on HIV treatment was equivalent to non-injectors. CD4 cell count, initial viral load, calendar year of commencing ART and age are more important determinants of AIDS and mortality than injecting status for in-treatment PLHIV in Victoria, Australia.

Beyond the intensive care unit bundle: Implementation of a successful hospital-wide initiative to reduce central line-associated bloodstream infections.

A multimodal hospital-wide central line-associated bloodstream infection (CLABSI) risk reduction strategy was implemented over a 20-month period at an Australian center. Reduced CLABSI rates were observed in both intensive care units (ICUs) (incidence rate ratio [IRR], 0.39; P < .001) and non-ICU wards (IRR, 0.54; P < .001). The median time to CLABSI onset was 7.5 days for ICU events and 13 days for non-ICU events. The timing of infection demonstrates the need for more careful attention to postinsertion care and access of central venous catheters.

Impact of chlorhexidine-impregnated washcloths on reducing incidence of vancomycin-resistant enterococci colonization in hematology-oncology patients.

BACKGROUND: Daily skin cleansing with washcloths impregnated with chlorhexidine gluconate (CHG) of patients in intensive care unit is associated with reduction in incidence of vancomycin-resistant Enterococci (VRE) acquisition. This study describes the impact on incidence of VRE colonization after the implementation of daily skin cleansing with 2% CHG-impregnated washcloths in hematology-oncology patients. METHODS: In this before-and-after study, we compared the incidence rate of VRE colonization during the baseline period (where routine soap-and-water bathing was used) with the intervention period where patients were cleansed with 2% CHG-impregnated washcloths. RESULTS: Acquisition of VRE decreased from 7.8% in the baseline to 3.8% in the intervention period (relative risk, 0.48, 95% confidence interval [CI], 0.21-1.09; P = .07). The crude relative rate of acquisition during the intervention period compared with the baseline period was 0.53 (95% CI, 0.23-1.23; P = .13). Patients who had been a roommate of a patient subsequently found to have VRE were at a significantly increased risk for acquiring VRE (hazard ratio, 18.8, 95% CI, 5.37-66.15; P < .001). However, patients admitted to the same bed number of previously known VRE-colonized patient were not at increased risk of VRE acquisition (hazard ratio, 0.37, 95% CI, 0.11-1.22; P = .10). CONCLUSION: We did not observe a statistically significant reduction in the rate of VRE colonization in association with the use of 2% CHG-impregnated washcloths among hematology-oncology patients.

Long-term survival in HIV positive patients with up to 15 Years of antiretroviral therapy.

BACKGROUND: Life expectancy has increased for newly diagnosed HIV patients since the inception of combination antiretroviral treatment (cART), but there remains a need to better understand the characteristics of long-term survival in HIV-positive patients. We examined long-term survival in HIV-positive patients receiving cART in the Australian HIV Observational Database (AHOD), to describe changes in mortality compared to the general population and to develop longer-term survival models. METHODS: Data were examined from 2,675 HIV-positive participants in AHOD who started cART. Standardised mortality ratios (SMR) were calculated by age, sex and calendar year across prognostic characteristics using Australian Bureau of Statistics national data as reference. SMRs were examined by years of duration of cART by CD4 and similarly by viral load. Survival was analysed using Cox-proportional hazards and parametric survival models. RESULTS: The overall SMR for all-cause mortality was 3.5 (95% CI: 3.0-4.0). SMRs by CD4 count were 8.6 (95% CI: 7.2-10.2) for CD4<350 cells/µl; 2.1 (95% CI: 1.5-2.9) for CD4 = 350-499 cells/µl; and 1.5 (95% CI: 1.1-2.0) for CD4≥500 cells/µl. SMRs for patients with CD4 counts <350 cells/µL were much higher than for patients with higher CD4 counts across all durations of cART. SMRs for patients with viral loads greater than 400 copies/ml were much higher across all durations of cART. Multivariate models demonstrated improved survival associated with increased recent CD4, reduced recent viral load, younger patients, absence of HBVsAg-positive ever, year of HIV diagnosis and incidence of ADI. Parametric models showed a fairly constant mortality risk by year of cART up to 15 years of treatment. CONCLUSION: Observed mortality remained fairly constant by duration of cART and was modelled accurately by accepted prognostic factors. These rates did not vary much by duration of treatment. Changes in mortality with age were similar to those in the Australian general population.

Prevalence and risk factors for VRE colonisation in a tertiary hospital in Melbourne, Australia: a cross sectional study.

BACKGROUND: Vancomycin-resistant Enterococcus (VRE) has been established as a significant health-care associated problem since its first isolation in Australia in 1994. In this study, we measured the point prevalence and identified risk factors associated with vanB VRE colonisation in a tertiary care hospital in Melbourne, Australia where VRE has been endemic for 15 years. METHODS: A hospital-wide point prevalence survey was conducted on October 13, 2008 with colonisation detected using rectal swab culture. Patient's demographic and medical information was collected through a review of medical records. Factors associated with VRE colonisation in univariate analysis were included in multivariate logistic regression model to adjust for confounding. RESULTS: The prevalence of VRE colonisation on the day of screening was 17.5% (95% CI, 13.7 to 21.9). VRE was detected from patients in each ward with the prevalence ranging from 3% to 29%. Univariate analysis showed the use of any antibiotic, meropenem, ciprofloxacin, diarrhoea and longer length of hospital stay were associated with increased risk of VRE colonisation (p<0.05). However, age, sex, proximity to VRE positive cases, use of other antibiotics including cephalosporins, vancomycin were not associated with increased risk (P>0.05). Multivariate analysis showed the exposure to meropenem (p=0.004), age (≥65 years) (p=0.036) and length of stay ≥7 days (p<0.001) as independent predictors of VRE colonisation. CONCLUSION: Our study suggests that exposure to antibiotics may have been more important than recent cross transmission for a high prevalence of vanB VRE colonisation at our hospital.

HIV seroconversions among male non-occupational post-exposure prophylaxis service users: a data linkage study.

BACKGROUND: Despite widespread prescription of non-occupational post-exposure prophylaxis (NPEP) in Victoria, little is known about subsequent HIV acquisition among NPEP users. We linked the Victorian NPEP Service (VNPEPS) database and the Victorian HIV Surveillance Registry to determine the number, incidence rate and predictive factors of HIV seroconversions among users of the VNPEPS. METHODS: Records from male patients that received NPEP in the VNPEPS database (n = 1420) between January 2001 and February 2008 were linked with all entries in the Victorian HIV Surveillance Registry up to May 2008. RESULTS: Sixty-one men who presented to the VNPEPS were identified as HIV seropositive; 16 of these were diagnosed at initial presentation for NPEP. The incidence of HIV seroconversion in males who were HIV seronegative at first presentation for NPEP was 1.27 (95% confidence interval 0.95-1.70) per 100 person-years. There was no association between HIV seroconversion and number of NPEP presentations or age. The median age of seroconversion was 34.6 years. CONCLUSION: The incidence of HIV infection among men presenting to the VNPEPS is slightly lower than the HIV incidence in NPEP users in a recent Australian cohort study of men who have sex with men, but higher than HIV incidence in general gay male populations. Frequency of NPEP use was not associated with risk of HIV seroconversion. Examination of risk behaviour before and after NPEP use in this population is required to further assess the impact of NPEP availability and use on HIV incidence rates and risk behaviour in Australia.

Hospitalizations in a cohort of HIV patients in Australia, 1999-2007.

OBJECTIVES: To describe hospitalization rates, risk factors and associated diagnoses in people with HIV in Australia between 1999 and 2007. DESIGN: Retrospective cohort study of people with HIV (n = 842) using data linkage between the Australian HIV Observational Database and administrative hospital morbidity data collections. METHODS: Incidence rate ratios with 95% confidence intervals were estimated using Poisson regression models to assess risk factors for hospitalization. Predictors of length of stay were assessed using generalized mixed models. The association between hospitalization and mortality was assessed using Cox regression. RESULTS: In 4519 person-years of observation, there were 2667 hospital admissions; incidence rate of 59 per 100 person-years. Hospitalization rates were 50-300% higher in this cohort than comparable age and sex strata in the general population. Older age (incidence rate ratio 1.46, 95% confidence interval 1.28-1.65 per 10-year increase) and prior AIDS (incidence rate ratio 1.71, 95% confidence interval 1.24-2.35) were significantly associated with hospitalization. Other predictors of hospitalization included lower CD4 cell counts, higher HIV RNA, longer duration of HIV infection and experience with more drug classes. Lower CD4 cell counts, older age and hepatitis C virus antibody positivity were independently associated with longer hospital stay. Non-AIDS diseases were the principle reason for admission in the majority of cases. Mortality was associated with more frequent hospitalization during the study period. CONCLUSION: Hospitalization rates are higher in people with HIV than the general population in Australia and are associated with markers of advanced HIV disease despite the widespread use of combination antiretroviral therapy.

Testing rates for sexually transmitted infections among HIV-infected men who have sex with men attending two different HIV services.

This study compares the testing rates of bacterial sexually transmitted infections (STIs) among HIV-positive men who have sex with men (MSM) attending two HIV clinics in Melbourne. Data on STI testing over a 12-month period were obtained for all HIV-positive MSM who attended the clinics between January and March 2006. Screening rates for bacterial STIs were significantly higher at a sexual health clinic (n = 254) compared with an infectious diseases clinic (n = 351), whether this was measured according to: at least one STI test being performed for chlamydia, gonorrhoea or syphilis (69% vs. 38%, P < 0.01); serological testing for syphilis alone (67% vs. 34%, P < 0.01); or 'complete' STI screening for pharyngeal gonorrhoea, urethral chlamydia, anal gonorrhoea, anal chlamydia and syphilis (41% vs. 6%, P < 0.01). Substantial differences in STI testing rates among HIV-positive MSM may exist between HIV clinical services depending on the measures in place that promote STI screening.

Reduction in hepatitis C-related liver disease associated with GB virus C in human immunodeficiency virus coinfection.

BACKGROUND & AIMS: It has been reported that GB virus C infection (GBV-C) leads to improved morbidity and mortality in patients with human immunodeficiency virus (HIV) infection. However, GBV-C has no effect on the course of liver disease in hepatitis C virus (HCV) monoinfection. The aim of the study was to determine the influence of GBV-C infection on liver disease in patients with HCV/HIV coinfection. METHODS: Data on 158 HCV/HIV patients were collected from January 1996 to October 2005. Two plasma specimens, collected at least 18 months apart, were tested for GBV-C RNA by reverse transcription-polymerase chain reaction with primers to the NS5B gene and confirmed using E2 gene primers and sequencing. Antibodies to GBV-C E2 protein were also determined. Liver-related morbidity and mortality were assessed from patient records. RESULTS: Fifty-seven of 158 (36%) patients had GBV-C RNA and 94 (59%) had evidence of exposure to GBV-C based on combined polymerase chain reaction and antibody results. Thirty-four (21%) patients had features of cirrhosis, with 20 having compensated and 14 having decompensated cirrhosis. Active GBV-C RNA was significantly associated with a reduction in cirrhosis, both compensated and decompensated in multivariate analysis (hazard ratio, 0.27; 95% confidence interval, 0.08-0.88; P = .03), as well as in analysis for cirrhosis-free survival vs duration of HCV infection (P = .006). No significant effect on liver-related or overall survival was observed. CONCLUSIONS: In these HCV/HIV-coinfected patients, GBV-C RNA was associated with a significant reduction in the severity of HCV-related liver disease.

Statins Blunt HAART-Induced CD4 T-Cell Gains but Have No Long-Term Effect on Virologic Response to HAART.

BACKGROUND: Statins are increasingly used in HIV-infected patients, but the effect of their immunomodulatory properties on antiretroviral-induced immune reconstitution is unknown. METHODS: The authors compared 6-month and 1-year changes in CD4 T-cell count, plasma HIV ribonucleic acid (RNA), and serum lipids in 69 HIV-infected patients receiving statins and 127 controls matched by age, nadir CD4 T-cell count, and hepatitis C serostatus. All patients were receiving highly active antiretroviral therapy (HAART). The authors used standard statistical tests for univariate comparisons and estimated average change in outcome measurements through repeated measures general linear models. RESULTS: Patients receiving statins had significantly higher median CD4 T-cell counts (430 vs 225 cells/microL, P < .001) and lower HIV RNA levels (2.3 vs 2.9 log10 copies/mL, P < .001) than controls. Statin-treated patients had diminished CD4 T-cell gain at 6 months, but this difference was not statistically significant at 12 months, despite similar 12-month virologic success rates. Patients receiving statins gained, on average, an estimated 60 fewer CD4 T-cells in the first 6 months than controls. CONCLUSIONS: Exposure to statins was associated with decreased CD4 T-cell gains during HAART in a cohort of HIV-infected patients, despite adequate virologic response. Studies with longer follow-up and detailed metabolic and immunologic monitoring are needed to confirm these findings and assess their significance and mechanisms.

Reduction in hospitalwide incidence of infection or colonization with methicillin-resistant Staphylococcus aureus with use of antimicrobial hand-hygiene gel and statistical process control charts.

OBJECTIVE: To evaluate the impact of serial interventions on the incidence of methicillin-resistant Staphylococcus aureus (MRSA). DESIGN: Longitudinal observational study before and after interventions. SETTING: The Alfred Hospital is a 350-bed tertiary referral hospital with a 35-bed intensive care unit (ICU). INTERVENTIONS: A series of interventions including the introduction of an antimicrobial hand-hygiene gel to the intensive care unit and a hospitalwide MRSA surveillance feedback program that used statistical process control charts but not active surveillance cultures. METHODS: Serial interventions were introduced between January 2003 and May 2006. The incidence and rates of new patients colonized or infected with MRSA and episodes of MRSA bacteremia in the intensive care unit and hospitalwide were compared between the preintervention and intervention periods. Segmented regression analysis was used to calculate the percentage reduction in new patients with MRSA and in episodes of MRSA bacteremia hospitalwide in the intervention period. RESULTS: The rate of new patients with MRSA in the ICU was 6.7 cases per 100 patient admissions in the intervention period, compared with 9.3 cases per 100 patient admissions in the preintervention period (P=.047). The hospitalwide rate of new patients with MRSA was 1.7 cases per 100 patient admissions in the intervention period, compared with 3.0 cases per 100 patient admissions in the preintervention period (P<.001). By use of segmented regression analysis, the maximum and conservative estimates for percentage reduction in the rate of new patients with MRSA were 79.5% and 42.0%, respectively, and the maximum and conservative estimates for percentage reduction in the rate of episodes of MRSA bacteremia were 87.4% and 39.0%, respectively. CONCLUSION: A sustained reduction in the number of new patients with MRSA colonization or infection has been demonstrated using minimal resources and a limited number of interventions.

A binational cohort study of ventilator-associated pneumonia in Denmark and Australia.

The objective was to determine the incidence and prognosis of ventilator-associated pneumonia (VAP) in intensive care units (ICUs) in Melbourne (29-bed ICU), Australia and Aarhus and Aalborg (22-bed unit and 8-bed ICU, respectively), Denmark and to characterize participating ICUs with regard to prevalence of nosocomial type bacterial pathogens, antibiotic resistance and antibiotic consumption. In this prospective cohort study 25 patients in Melbourne and 32 patients in Aarhus + Aalborg had a first episode of VAP. The incidence of VAP per 1000 ventilator d was 6.2 in Melbourne and 9.5 in Aarhus + Aalborg. Case fatality during hospital admission was 28% and 59%, respectively (unadjusted odds ratio (OR) 0.3, 95% confidence interval (CI) 0.1-0.8). OR adjusted for age and APACHE II score was 0.2 (95% CI 0.1-1.0). Nosocomial type pathogens including methicillin resistant Staphylococcus aureus were more prevalent in Melbourne, and antibiotic consumption per VAP patient was 35% higher in Melbourne than in Aarhus + Aalborg. To judge from the present data, there seems to be a complicated interrelationship between prognosis on the 1 hand and antibiotic consumption and resistance on the other. A more favourable prognosis was found in Melbourne, where levels of antibiotic consumption and antimicrobial resistance were higher than in Aarhus + Aalborg.

Surgical-site infection rates and risk factor analysis in coronary artery bypass graft surgery.

BACKGROUND: The Victorian Infection Control Surveillance Project (VICSP) is a multicenter collaborative surveillance project established by infection control practitioners. Five public hospitals contributed data for patients undergoing coronary artery bypass graft (CABG) surgery. OBJECTIVE: To determine the aggregate and comparative interhospital surgical-site infection (SSI) rates for patients undergoing CABG surgery and the risk factors for SSI in this patient group. METHOD: Each institution used standardized definitions of SSI, risk adjustment, and reporting methodology according to the National Nosocomial Infections Surveillance System of the Centers for Disease Control and Prevention. Data on potential risk factors were prospectively collected. RESULTS: For 4,474 patients undergoing CABG surgery, the aggregate SSI rate was 7.8 infections per 100 procedures (95% confidence interval [CI95], 7.0-8.5), with individual institutions ranging between 4.5 and 10.7 infections per 100 procedures. Multivariate risk factor analysis demonstrated age (odds ratio [OR], 1.02; CI95, 1.01-1.04; P < .001), obesity (OR, 1.8; CI95, 1.4-2.3; P < .001), and diabetes mellitus (OR, 1.6; CI95, 1.2-2.1; P < .001) as independent predictors of SSI. Three hundred thirty-four organisms were isolated from 296 SSIs. Of the total SSIs, methicillin-resistant Staphylococcus aureus was isolated from 32%, methicillin-sensitive S. aureus from 24%, gram-negative bacilli (eg, Enterobacter and Escherichia coli) from 18%, and miscellaneous organisms from the remainder. CONCLUSION: We documented aggregate and comparative SSI rates among five Victorian public hospitals performing CABG surgery and defined specific independent risk factors for SSI. VICSP data offer opportunities for targeted interventions to reduce SSI following cardiac surgery.