Ann L. Bull

Identification of a Drosophila gene encoding a calmodulin-binding protein with homology to the trp phototransduction gene

We have isolated a number of Drosophila cDNAs on the basis of their encoding calmodulin-binding proteins. A full-length cDNA clone corresponding to one of these genes has been cloned and sequenced. Conservation of amino acid sequence and tissue-specific expression are observed between this gene and the transient receptor potential (trp) gene. We propose the name transient receptor potential-like (trpl) to describe this newly isolated gene. The trpl protein contains two possible calmodulin-binding sites, six transmembrane regions, and a sequence homologous to an ankyrin-like repeat. Structurally, the trpl and trp proteins resemble cation channel proteins, particularly the brain isoform of the voltage-sensitive Ca2+ channel. The identification of a protein similar to the trp gene product, yet also able to bind Ca2+/calmodulin, allows for a reinterpretation of the phenotype of the trp mutations and suggests that both genes may encode light-sensitive ion channels.

An alternative scoring system to predict risk for surgical site infection complicating coronary artery bypass graft surgery

OBJECTIVE To analyze the risk factors for surgical site infection (SSI) complicating coronary artery bypass graft (CABG) surgery and to create an alternative SSI risk score based on the results of multivariate analysis. METHODS A prospective cohort study involving inpatient and laboratory-based surveillance of patients who underwent CABG surgery over a 27-month period from January 1, 2003 through March 31, 2005. Data were obtained from 6 acute care hospitals in Victoria, Australia, that contributed surveillance data for SSI complicating CABG surgery to the Victorian Hospital Acquired Infection Surveillance System Coordinating Centre and the Australasian Society of Cardiac and Thoracic Surgeons, also in Victoria. RESULTS A total of 4,633 (93%) of the 4,987 patients who underwent CABG surgery during this period were matched in the 2 systems databases. There were 286 SSIs and 62 deep or organ space sternal SSIs (deep or organ space sternal SSI rate, 1.33%). Univariate analysis revealed that diabetes mellitus, body mass index (BMI) greater than 35, and receipt of blood transfusion were risk factors for all types of SSI complicating CABG surgery. Six multivariate analysis models were created to examine either preoperative factors alone or preoperative factors combined with operative factors. All models revealed diabetes and BMI of 30 or greater as risk factors for SSI complicating CABG surgery. A new preoperative scoring system was devised to predict sternal SSI, which assigned 1 point for diabetes, 1 point for BMI of 30 or greater but less than 35, and 2 points for BMI of 35 or greater. Each point in the scoring system represented approximately a doubling of risk of SSI. The new scoring system performed better than the National Nosocomial Infections Surveillance System (NNIS) risk index at predicting SSI. CONCLUSION A new weighted scoring system based on preoperative risk factors was created to predict sternal SSI risk following CABG surgery. The new scoring system outperformed the NNIS risk index. Future studies are needed to validate this scoring system.

Increasing incidence of Clostridium difficile infection, Australia, 2011-2012

Objectives: To report the quarterly incidence of hospital‐identified Clostridium difficile infection (HI‐CDI) in Australia, and to estimate the burden ascribed to hospital‐associated (HA) and community‐associated (CA) infections.

Validation of Statewide Surveillance System Data on Central Line–Associated Bloodstream Infection in Intensive Care Units in Australia

OBJECTIVE To measure the interobserver agreement, sensitivity, specificity, positive predictive value, and negative predictive value of data submitted to a statewide surveillance system for identifying central line-associated bloodstream infection (BSI). DESIGN Retrospective review of hospital medical records comparing reported data with gold standard according to definitions of central line-associated BSI. SETTING Six Victorian public hospitals with more than 100 beds. METHODS Reporting of surveillance outcomes was undertaken by infection control practitioners at the hospital sites. Retrospective evaluation of the surveillance process was carried out by independent infection control practitioners from the Victorian Hospital Acquired Infection Surveillance System (VICNISS). A sample of records of patients reported to have a central line-associated BSI were assessed to determine whether they met the definition of central line-associated BSI. A sample of records of patients with bacteremia in the intensive care unit during the assessment period who were not reported as having central line-associated BSI were also assessed to see whether they met the definition of central line-associated BSI. RESULTS Records of 108 patients were reviewed; the agreement between surveillance reports and the VICNISS assessment was 67.6% (k = 0.31). Of the 46 reported central line-associated BSIs, 27 were confirmed to be central line-associated BSIs, for a positive predictive value of 59% (95% confidence interval [CI], 43%-73%). Of the 62 cases of bacteremia reviewed that were not reported as central line-associated BSIs, 45 were not associated with a central line, for a negative predictive value of 73% (95% CI, 60%-83%). Estimated sensitivity was 35%, and specificity was 87%. The positive likelihood ratio was 3.0, and the negative likelihood ratio was 0.72. DISCUSSION The agreement between the reporting of central line-associated BSI and the gold standard application of definitions was unacceptably low. False-negative results were problematic; more than half of central line-associated BSIs may be missed in Victorian public hospitals.

Impact of vancomycin surgical antibiotic prophylaxis on the development of methicillin-sensitive staphylococcus aureus surgical site infections: report from Australian Surveillance Data (VICNISS).

Objective:To compare risks for developing surgical site infection (SSI) due to Staphylococcus aureus when vancomycin is used for antibiotic prophylaxis with risks when a &bgr;-lactam antibiotic is administered for prophylaxis. Background:Vancomycin is often used as surgical antibiotic prophylaxis for major surgery. In nonsurgical populations, there is evidence that vancomycin is less effective for prevention and treatment of methicillin-sensitive Staphylococcus aureus (MSSA) infections. Since 2002, the Victorian Healthcare Associated Surveillance System (VICNISS) has used standardized methods for infection surveillance in Australia, including any prophylactic antibiotic agent administered before surgical procedures. Methods:Surveillance records were obtained for patients undergoing 4 clean surgical procedures during the period of November 2002 to June 2009. Logistic regression analysis was used to examine risk factors for infection, including age, procedure duration, American Society of Anesthesiologists score, and choice and timing of antibiotic prophylaxis. Results:The data set consisted of 22,549 procedures, including cardiac bypass and hip and knee arthroplasty procedures. Vancomycin prophylaxis was administered in 1610 cases and a &bgr;-lactam antibiotic for 20,939 cases. A total of 754 SSIs were recorded. The most frequent pathogens were MSSA, methicillin-resistant Staphylococcus aureus, and Pseudomonas species. The adjusted odds ratio (OR) for an SSI with MSSA was 2.79, where vancomycin prophylaxis was administered (P < 0.001). For methicillin-resistant Staphylococcus aureus infection, the adjusted OR for vancomycin was 0.44 (P = 0.05), whereas for Pseudomonas infection, it was 0.96 (P = 0.95). Conclusions:In a large Australian study population, prophylaxis with vancomycin was found to be associated with an increased risk of SSI due to MSSA when compared with prophylaxis with a &bgr;-lactam antibiotic. Given the potential for poorer surgical outcomes in the setting of indiscriminate prophylactic vancomycin use, measures to improve adherence to guidelines for restricted administration of prophylactic vancomycin are supported.

Impact of revising the National Nosocomial Infection Surveillance System definition for catheter-related bloodstream infection in ICU: reproducibility of the National Healthcare Safety Network case definition in an Australian cohort of infection control professionals

BACKGROUND Effective and comparable surveillance for central venous catheter-related bloodstream infections (CLABSIs) in the intensive care unit requires a reproducible case definition that can be readily applied by infection control professionals. METHODS Using a questionnaire containing clinical cases, reproducibility of the National Nosocomial Infection Surveillance System (NNIS) surveillance definition for CLABSI was assessed in an Australian cohort of infection control professionals participating in the Victorian Hospital Acquired Infection Surveillance System (VICNISS). The same questionnaire was then used to evaluate the reproducibility of the National Healthcare Safety Network (NHSN) surveillance definition for CLABSI. Target hospitals were defined as large metropolitan (1A) or other large hospitals (non-1A), according to the Victorian Department of Human Services. Questionnaire responses of Centers for Disease Control and Prevention NHSN surveillance experts were used as gold standard comparator. RESULTS Eighteen of 21 eligible VICNISS centers participated in the survey. Overall concordance with the gold standard was 57.1%, and agreement was highest for 1A hospitals (60.6%). The proportion of congruently classified cases varied according to NNIS criteria: criterion 1 (recognized pathogen), 52.8%; criterion 2a (skin contaminant in 2 or more blood cultures), 83.3%; criterion 2b (skin contaminant in 1 blood culture and appropriate antimicrobial therapy instituted), 58.3%; non-CLABSI cases, 51.4%. When survey questions regarding identification of cases of CLABSI criterion 2b were removed (consistent with the current NHSN definition), overall percentage concordance increased to 62.5% (72.2% for 1A centers). CONCLUSION Further educational interventions are required to improve the discrimination of primary and secondary causes of bloodstream infection in Victorian intensive care units. Although reproducibility of the CLABSI case definition is relatively poor, adoption of the revised NHSN definition for CLABSI is likely to improve the concordance of Victorian data with international centers.

Performance of the National Nosocomial Infections Surveillance Risk Index in Predicting Surgical Site Infection in Australia

BACKGROUND The Victorian Hospital Acquired Infection Surveillance System (VICNISS) hospital-acquired infection surveillance system was established in 2002 in Victoria, Australia, and collates surgical site infection (SSI) surveillance data from public hospitals in Australia. OBJECTIVE To evaluate the association between the US National Nosocomial Infections Surveillance (NNIS) systems risk index and SSI rates for 7 surgical procedures. METHODS SSI surveillance was performed with NNIS definitions and methods for surgical procedures performed between November 2002 and September 2004. Correlations were assessed using the Goodman-Kruskal gamma statistic. RESULTS Data were submitted for the following numbers of procedures: appendectomy, 545; coronary artery bypass graft (CABG), 4,632; cholecystectomy, 1,001; colon surgery, 623; cesarean section, 4,857; hip arthroplasty, 3,825; and knee arthroplasty, 2,416. NNIS risk index and increasing SSI rate were moderately well correlated for appendectomy ( gamma =0.55), colon surgery ( gamma =0.48), and cesarean section ( gamma =0.42). A fairly positive correlation was found for cholecystectomy ( gamma =0.17), hip arthroplasty ( gamma =0.2), and knee arthroplasty ( gamma =0.16). However, for CABG surgery, a poor association was found ( gamma =0.02). CONCLUSIONS The NNIS risk index was positively correlated with an increasing SSI rate for all 7 procedures; the strongest correlation was found for appendectomy, cesarean section, and colon surgery, and the poorest correlation was found for CABG surgery. We believe that risk stratification with the NNIS risk index is appropriate for comparison of data for most procedures and superior to use of no risk adjustment. However, for some procedures, particularly CABG, further studies of alternative risk indexes are needed to better stratify patients.

Validation of Coronary Artery Bypass Graft Surgical Site Infection Surveillance Data From a Statewide Surveillance System in Australia

OBJECTIVE To measure the accuracy and determine the positive predictive value (PPV) and negative predictive value (NPV) of data submitted to a statewide surveillance system for identifying surgical site infection (SSI) complicating coronary artery bypass graft (CABG) surgery. DESIGN Retrospective review of hospital medical records comparing SSI data with surveillance data submitted by infection control consultants (ICCs). SETTING Victorian Hospital Acquired Infection Surveillance System (VICNISS) Coordinating Centre in Victoria, Australia. PATIENTS All patients reported to have an SSI following CABG surgery and a random sample of approximately 10% of patients reported not to have an SSI following CABG surgery. RESULTS The VICNISS ascertainment rate for CABG procedures in Victoria was 95%. One hundred sixty-nine medical records were reviewed, and reviewers agreed with ICCs about 46 (96%) of the patients reported as infected by the ICCs and 31 (91%) of the patients identified with a sternal SSI by the ICCs. In one-third of SSIs, the depth of SSI documented by ICCs was discordant with that documented by the reviewers. Disagreement about patients with donor site SSI was frequent. When the review findings were used as the reference standard, the PPV for ICC-reported SSI was 96% (95% confidence interval [CI], 86%-99%), and the NPV was 97% (95% CI, 92%-99%). For ICC-reported sternal SSI, the PPV was 91% (95% CI, 76%-98%) and the NPV was 98% (95% CI, 94%-100%). CONCLUSIONS There was broad agreement on the number of infected patients and the number of patients with sternal SSI. However, discordance was frequent with respect to the depth of sternal SSI and the identification of donor site SSI. We recommend modifications to the methodology for National Nosocomial Infection Surveillance System-based surveillance for SSI following CABG surgery.

Estimating sensitivity and specificity from positive predictive value, negative predictive value and prevalence: application to surveillance systems for hospital-acquired infections.

Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) are terms usually associated with diagnostic testing. Although these concepts have been expanded from diagnostic assays to surveillance systems, these systems are not like diagnostic assays. In attempting to estimate the sensitivity and specificity of surveillance systems, situations may arise where only the PPV, NPV and prevalence are known. We aim to demonstrate the equivalence of two methods for calculating sensitivity and specificity from PPV, NPV and prevalence. The formulae for sensitivity and specificity are calculated from first principles and compared with the adjustment of a standard contingency table. We have illustrated this method using a review of a sample of surgical site infection cases following coronary artery bypass grafting. The derived prevalence from the sample is an estimate of the population prevalence and is the value that must be used in the formulae for sensitivity and specificity as functions of PPV, NPV and prevalence to obtain the same estimates as those obtained from the adjusted contingency table. The general proof of this principle is provided as an Appendix. The sensitivity and specificity of surveillance systems can be calculated by two equivalent methods when only PPV, NPV and prevalence are known.

Diminishing Surgical Site Infections in Australia: Time Trends in Infection Rates, Pathogens and Antimicrobial Resistance Using a Comprehensive Victorian Surveillance Program, 2002–2013

OBJECTIVE To evaluate time trends in surgical site infection (SSI) rates and SSI pathogens in Australia. DESIGN Prospective multicenter observational cohort study. SETTING A group of 81 Australian healthcare facilities participating in the Victorian Healthcare Associated Infection Surveillance System (VICNISS). PATIENTS All patients underwent surgeries performed between October 1, 2002, and June 30, 2013. National Healthcare Safety Network SSI surveillance methods were employed by the infection prevention staff at the participating hospitals. INTERVENTION Procedure-specific risk-adjusted SSI rates were calculated. Pathogen-specific and antimicrobial-resistant (AMR) infections were modeled using multilevel mixed-effects Poisson regression. RESULTS A total of 183,625 procedures were monitored, and 5,123 SSIs were reported. Each year of observation was associated with 11% risk reduction for superficial SSI (risk ratio [RR], 0.89; 95% confidence interval [CI], 0.88-0.90), 9% risk reduction for deep SSI (RR, 0.91; 95% CI, 0.90-0.93), and 5% risk reduction for organ/space SSI (RR, 0.95; 95% CI, 0.93-0.97). Overall, 3,318 microbiologically confirmed SSIs were reported. Of these SSIs, 1,174 (35.4%) were associated with orthopedic surgery, 827 (24.9%) with coronary artery bypass surgery, 490 (14.8%) with Caesarean sections, and 414 (12.5%) with colorectal procedures. Staphylococcus aureus was the most frequently identified pathogen, and a statistically significant increase in infections due to ceftriaxone-resistant Escherichia coli was observed (RR, 1.37; 95% CI, 1.10-1.70). CONCLUSIONS Standardized SSI surveillance methods have been implemented in Victoria, Australia. Over an 11-year period, diminishing rates of SSIs have been observed, although AMR infections increased significantly. Our findings facilitate the refinement of recommended surgical antibiotic prophylaxis regimens and highlight the need for a more expansive national surveillance strategy to identify changes in epidemiology.