STOP Signs: A Population-based Interrupted Time Series Analysis of Antibiotic Duration for Complicated Intraabdominal Infection Before and After the Publication of a Landmark RCT.

OBJECTIVE: To determine if the STOP-IT randomized controlled trial changed antibiotic prescribing in patients with Complicated Intraabdominal Infection (CIAI). SUMMARY OF BACKGROUND DATA: CIAI is common and causes significant morbidity. In May 2015, the STOP-IT randomized controlled trial showed equivalent outcomes between four-day and clinically determined antibiotic duration. METHODS: This was a population-based retrospective cohort study using interrupted time series methods. The STOP-IT publication date was the exposure. Median duration of inpatient antibiotic prescription was the outcome. All adult patients admitted to four hospitals in Calgary, Canada between July 2012 and December 2018 with CIAI who survived at least four days following source control were included. Analysis was stratified by infectious source as appendix or biliary tract (group A) versus other (group B). RESULTS: Among 4384 included patients, clinical and demographic attributes were similar before vs after publication. In Group A, median inpatient antibiotic duration was 3 days and unchanged from the beginning to the end of the study period [adjusted median difference -0.00 days, 95% confidence interval (CI) -0.37 - 0.37 days]. In Group B, antibiotic duration was shorter at the end of the study period (7.87 vs 6.73 days; -1.14 days, CI-2.37 - 0.09 days), however there was no change in trend following publication (-0.03 days, CI -0.16 - 0.09). CONCLUSIONS: For appendiceal or biliary sources of CIAI, antibiotic duration was commensurate with the experimental arm of STOP-IT. For other sources, antibiotic duration was long and did not change in response to trial publication. Additional implementation science is needed to improve antibiotic stewardship.

Staphylococcus aureus in Non-Cystic Fibrosis Bronchiectasis: Prevalence and Genomic Basis of High Inoculum ß-Lactam Resistance.

Rationale: The pathobiology of Staphylococcus aureus in non-cystic fibrosis bronchiectasis (nCFB) is poorly defined. When present at high density or "inoculum," some methicillin-sensitive S. aureus (MSSA) can inefficiently degrade antistaphylococcal ß-lactam antibiotics via BlaZ penicillinases (termed the "inoculum effect" [IE]). Given the high burden of organisms in bronchiectatic airways, this is particularly relevant. Objectives: Drawing from a prospectively collected biobank, we sought to understand the prevalence, natural history, potential for transmission, and antibiotic resistance profiles among nCFB-derived MSSA isolates. Methods: All individuals attending a regional consultancy nCFB clinic with sputum collected between 1981 and 2017 were considered, and those with one or more S. aureus-positive cultures composed the cohort. Each individual's most recent biobank isolate was subjected to whole-genome sequencing (including the blaZ gene), antibacterial susceptibility testing, and comparative ß-lactam testing at standard (5 × 105 colony-forming unit [cfu]/ml) and high (5 × 107 cfu/ml) inocula to assess for the IE and pronounced IE. Results: Seventy-four (35.4%) of 209 individuals had one or more sputum samples with S. aureus (68 MSSA, 6 methicillin-resistant S. aureus). Those with S. aureus infection were more likely to be female. Among 60 of 74 MSSA isolates subjected to whole-genome sequencing, no evidence of transmission was identified, although specific multilocus sequence typing types were prevalent, including ST-1, ST-15, ST-30, and ST-45. Antibiotic resistance was uncommon, except for macrolides (∼20%). Among the 60 MSSA samples, the prevalence of IE and pronounced IE was observed to be drug specific: meropenem (0% and 0%, respectively), cefepime (3% and 5%, respectively), ceftazidime (8% and 0%, respectively), cloxacillin (12% and 0%, respectively), cefazolin (23% and 0%, respectively), and piperacillin-tazobactam (37% and 17%, respectively). The cefazolin IE was associated with blaZ type A (P < 0.01) and ST-30 (P < 0.01), whereas the piperacillin-tazobactam IE was associated with type C blaZ (P < 0.001) and ST-15 (P < 0.05). Conclusions:S. aureus infection was common, although no evidence of transmission was apparent in our nCFB cohort. Although routine susceptibility testing did not identify significant resistance, inoculum-related resistance was found to be relevant for commonly used nCFB antibiotics, including cefazolin and piperacillin-tazobactam. Given previous associations between IEs and negative patient outcomes, further work is warranted to understand how this phenotype impacts nCFB disease progression.

Epidemiology and risk factors for pyogenic liver abscess in the Calgary Health Zone revisited: a population-based study.

BACKGROUND: Pyogenic liver abscess (PLA), although uncommon in North America, is associated with significant morbidity and mortality. We sought to re-examine the epidemiology, risk factors, and outcomes of PLA in a large, diverse Canadian health zone. METHODS: All Calgary Health Zone (CHZ) residents aged ≥20 with PLA between 2015 and 2017 were identified. Incidence and mortality rates were calculated using census data. Risk factors for PLA were identified using a multivariate analysis. Data was compared to 1999-2003 data, also collected in the CHZ. RESULTS: There were 136 patients diagnosed with PLA between 2015 and 2017. Incidence rate during this period increased significantly relative to 1999-2003 (3.7 vs 2.3 cases/100,000 population, p < 0.01), however, mortality rates remained similar. The microbiological composition of PLA did not change over this 15-year time period but the number of antimicrobial resistant isolates did increase (8% vs 1%, p = 0.04). The greatest risk factors for PLA relative to general populations included current malignancy, liver-transplant, end-stage renal disease, and cirrhosis. Thirty-day mortality was 7.4% and independent risk factors included polymicrobial bacteremia, absence of abscess drainage, congestive-heart failure, a history of liver disease, and admission bilirubin. CONCLUSIONS: Pyogenic liver abscess is a health concern with rising incidence rate. The increasing prevalence of comorbidities in our population and factors that are associated with risk of PLA suggests this will continue to be an emerging diagnosis of concern. Increasing prevalence of antibiotic resistant organisms compounding unclear optimal treatment regimens is an issue that requires urgent study.

Forgoing transesophageal echocardiogram in selected patients with complicated Staphylococcus aureus bacteremia.

Infective endocarditis (IE) has been increasingly recognized as an important complication of Staphylococcus aureus bacteremia (SAB), leading to a low threshold for echocardiography and extended treatment with anti-staphylococcal agents. However, outside of IE, many indications for prolonged anti-staphylococcal therapy courses are present. We sought to determine the frequency in which findings from a transesophageal echocardiogram (TEE) changed clinical SAB management in a large Canadian health region. Residents (> 18 years) with SAB from 2012 to 2014 who underwent transthoracic echocardiogram (TTE) and TEE were assessed. Patients potentially benefiting from an extended course of anti-staphylococcal agents were defined a priori. Patient demographics, treatment (including surgical), and clinical outcomes were extracted and evaluated. Of the 705 episodes of SAB that underwent a screening echocardiogram, 203 episodes underwent both a TTE and TEE, of which 92.1% (187/203) contained an a priori indication for extended anti-staphylococcal therapy. Regardless of TEE results, actual duration of therapy did not differ in SAB episodes that had ≥ 1 extended anti-staphylococcal therapy criteria (36.7 days, IQR 23.4-48.6 vs. 43.8 days, IQR 33.3-49.5, p = 0.17). Additionally, there were no cases in which TEE was utilized as the sole reason to shorten duration of therapy or proceed to surgery for those with SAB. Routine performance of TEE may be unnecessary in all SAB as many patients have pre-existing indications for extended anti-staphylococcal therapy independent of TEE findings. An algorithm to selectively identify cases of SAB that would benefit from TEE can reduce resource and equipment expenditure and patient risks associated with TEE.

High incidence of Pneumocystis jirovecii pneumonia in allogeneic hematopoietic cell transplant recipients in the modern era.

BACKGROUND: International guidelines for Pneumocystis jirovecii pneumonia (PJP) prevention recommend prophylaxis for ≥6 months following allogeneic hematopoietic cell transplantation, and longer in patients with graft-versus-host disease (GVHD) or on immunosuppressive therapy (IST). These recommendations are based on cohorts of patients who did not routinely receive anti-thymocyte globulin (ATG) for GVHD prophylaxis. METHODS: We performed a retrospective chart review of 649 patients, all of whom received ATG as part of GVHD prophylaxis. RESULTS: The cumulative incidence of definite PJP was 3.52% at both 3 and 5 years (median follow up, 1648 days for survivors). PJP occurred in 13 non-GVHD patients between days 207 and 508, due in part to low CD4 T-cell counts (<200 CD4 T cells/µL). PJP occurred in eight GVHD patients between days 389 and 792, due in part to non-adherence to PJP prophylaxis guidelines (discontinuation of PJP prophylaxis at <3 months after discontinuation of IST). Breakthrough PJP infection was not observed in patients receiving prophylaxis with cotrimoxazole, dapsone or atovaquone, whereas three cases were observed with inhaled pentamidine. DISCUSSION: In conclusion, for non-GVHD patients receiving ATG-containing GVHD prophylaxis, 6 months of PJP prophylaxis is inadequate, particularly if the CD4 T-cell count is <200 cells/µL or if there is a high incidence of PJP in the community. For patients with GVHD receiving ATG-containing GVHD prophylaxis, continuing PJP prophylaxis until ≥3 months post-discontinuation of IST is important. Cotrimoxazole, dapsone and atovaquone are preferred over inhaled pentamidine.

Evaluation of Simplexa Group A Strep Direct Kit Compared to Hologic Group A Streptococcal Direct Assay for Detection of Group A Streptococcus in Throat Swabs.

Diagnosis of bacterial pharyngitis is confirmed by detection of group A Streptococcus (GAS) in patient throat samples. Testing of throat samples has historically relied on culture, but new molecular methods allow much faster test turnaround time (i.e., same day versus 48 to 72 h for culture). Our laboratory uses the Hologic GAS Direct (GASD) assay for screening more than 125,000 throat samples per year. Simplexa GAS Direct is a new real-time quantitative PCR (qPCR) assay that does not require initial DNA extraction. Performance of Simplexa qPCR was compared to GASD. A total of 289 throat swabs were collected from patients attending ambulatory clinics in Calgary, Alberta, Canada. A total of 60 (20.8%) of the samples were initially GAS positive by either method: 54 by both methods, 4 by Simplex qPCR alone, and 2 by GASD alone. An in-house PCR using a unique GAS primer set was used to resolve the 6 discrepant results. Overall, GASD compared to Simplexa qPCR had a sensitivity, specificity, positive predictive value, and negative predictive value of 93.1% versus 100%, 100% versus 100%, 100% versus 100%, and 98.31% versus 100%, respectively. Implementation of Simplexa qPCR in our laboratory setting would cost more but allow the high sample volume to be reported in half the time and save 0.62 medical laboratory technician (MLT) full-time equivalent (FTE). In comparison to culture, the implementation of Simplexa qPCR would save 2.79 medical laboratory assistant (MLA) FTE plus 0.94 MLT FTE. Simplexa qPCR has improved performance and diagnostic efficiency in a high-volume laboratory compared to GASD for GAS detection in throat swabs.

Evaluation of StrepBSelect Chromogenic Medium and the Fast-Track Diagnostics Group B Streptococcus (GBS) Real-Time PCR Assay Compared to Routine Culture for Detection of GBS during Antepartum Screening.

Life-threatening infection in neonates due to group B Streptococcus (GBS) is preventable by screening of near-term pregnant women and treatment at delivery. A total of 295 vaginal-rectal swabs were collected from women attending antepartum clinics in Calgary, Alberta, Canada. GBS colonization was detected by the standard culture method (Strep B Carrot Broth subcultured to blood agar with a neomycin disk) and compared to recovery with Strep Group B Broth (Dalynn Biologicals) subcultured to StrepBSelect chromogenic medium (CM; Bio-Rad Laboratories) and the Fast-Track Diagnostics GBS real-time PCR (quantitative PCR [qPCR]) assay (Phoenix Airmid Biomedical Corp.) performed with broth-enriched samples and the Abbott m2000sp/m2000rt system. A total of 62/295 (21%) women were colonized with GBS; 58 (19.7%) cases were detected by standard culture, while CM and qPCR each found 61 (20.7%) cases. The qPCR and CM were similar in performance, with sensitivities, specificities, and positive and negative predictive values of 98.4 and 98.4%, 99.6 and 99.6%, 98.4 and 98.4%, and 99.6 and 99.6%, respectively, compared to routine culture. Both qPCR and CM would allow more rapid reporting of routine GBS screening results than standard culture. Although the cost per test was similar for standard culture and CM, the routine use of qPCR would cost approximately four times as much as culture-based detection. Laboratories worldwide should consider implementing one of the newer methods for primary GBS testing, depending on the cost limitations of different health care jurisdictions.

Incidence, risk factors, and outcomes of Fusobacterium species bacteremia.

BACKGROUND: Fusobacterium species (spp.) bacteremia is uncommon and has been associated with a variety of clinical presentations. We conducted a retrospective, population based study to determine the relative proportion of species in this genus causing bacteremia and the risk factors for infection and adverse clinical outcomes. METHODS: All cases of Fusobacterium spp. bacteremia detected at a regional microbiology laboratory serving outpatient and acute care for a population of approximately 1.3 million people over 11 years were identified from a computerized database. Clinical data on these cases was extracted from an administrative database and analyzed to determine underlying risk factors for and outcomes of infection. RESULTS: There were 72 incident cases of Fusobacterium spp. bacteremia over the study period (0.55 cases/100,000 population per annum). F. nucleatum was the most frequent species (61%), followed by F. necrophorum (25%). F. necrophorum bacteremia occurred in a younger population without underlying comorbidities and was not associated with mortality. F. nucleatum bacteremia was found in an older population and was associated with underlying malignancy or receiving dialysis. Death occurred in approximately 10% of F. nucleatum cases but causality was not established in this study. CONCLUSIONS: Fusobacterium spp. bacteremia in our community is uncommon and occurs in approximately 5.5 cases per million population per annum. F. necrophorum occurred in an otherwise young healthy population and was not associated with any mortality. F. nucleatum was found primarily in older patients with chronic medical conditions and was associated with a mortality of approximately 10%. Bacteremias from other Fusobacterium spp. were rare.

Evaluation of the Xpert® group B streptococcus real-time polymerase chain reaction assay compared to StrepB Carrot Broth™ for the rapid intrapartum detection of group B streptococcus colonization.

Xpert group B streptococcus (GBS) was compared to StrepB Carrot Broth™ (SCB) for the detection of intrapartum GBS colonization by dually collecting vaginal/rectal swabs from 231 women. Xpert GBS detected all of the cases (45, 19.5%), but 4 were missed by SCB. A rapid Xpert GBS service for women in labor would increase costs by ∼$55.000 per annum in our region.

Immunoglobulin A-dominant postinfectious glomerulonephritis: frequent occurrence in nondiabetic patients with Staphylococcus aureus infection.

Immunoglobin A-dominant postinfectious glomerulonephritis is a distinct clinicopathologic entity that has been linked to staphylococcal infection, including methicillin-resistant Staphylococcus aureus. An association with diabetic nephropathy has been suggested. Although the morphologic features resemble other forms of postinfectious glomerulonephritis, immunofluorescence shows dominant or codominant immunoglobulin A immune-complex deposits. We encountered 7 patients with immunoglobulin A-dominant postinfectious glomerulonephritis over 2½ years at a single center. All patients presented with renal failure and with varying degrees of hematuria, proteinuria, and hypertension. All patients had clinical infections at the time of presentation. Four patients had documented S aureus infections. Three patients had methicillin-resistant S aureus infection within 2 weeks before the renal biopsy; 2 of these had an infection with a community-associated methicillin-resistant S aureus-10 clone, equivalent to USA300. One patient had methicillin-sensitive S aureus infection. Diffuse proliferative endocapillary glomerulonephritis was found in all cases; 1 had a membranoproliferative glomerulonephritic pattern, and 1 patient had a crescentic glomerulonephritis. Immunofluorescence microscopy showed dominant immunoglobulin A subepithelial and mesangial immune complexes in 5 patients and codominant immunoglobulin A with immunoglobulin G in 2 patients. Electron microscopy revealed large subepithelial deposits ("humps") in all cases. Only 1 patient had clinical diabetes mellitus but without biopsy-proven diabetic nephropathy. Two patients died, including the patient with diabetes mellitus. Renal function improved after therapy in 5 nondiabetic patients, but full recovery was not seen during the follow-up. We confirm that immunoglobulin A-dominant postinfectious glomerulonephritis is often associated with S aureus and methicillin-resistant S aureus infections, and, for the first time, we document an association with community-associated methicillin-resistant S aureus.

McKay agar enables routine quantification of the 'Streptococcus milleri' group in cystic fibrosis patients.

The 'Streptococcus milleri' group (SMG) has recently been recognized as a contributor to bronchopulmonary disease in cystic fibrosis (CF). Routine detection and quantification is limited by current CF microbiology protocols. McKay agar was developed previously for the semi-selective isolation of this group. Here, McKay agar was validated against a panel of clinical SMG isolates, which revealed improved SMG recovery compared with Columbia blood agar. The effectiveness of this medium was evaluated by appending it to the standard CF sputum microbiology protocols in a clinical laboratory for a 6-month period. All unique colony types were isolated and identified by 16S rRNA gene sequencing. Whilst a wide variety of organisms were isolated, members of the SMG were the most prevalent bacteria cultured, and McKay agar allowed routine quantification of the SMG from 10(3) to >10(8) c.f.u. ml(-1) directly from sputum. All members of the SMG were detected [Streptococcus anginosus (40.7 %), Streptococcus intermedius (34.3 %) and Streptococcus constellatus (25 %)] with an overall prevalence rate of 40.6 % in our adult CF population. Without exception, samples where SMG isolates were cultured at 10(7) c.f.u. ml(-1) or greater were associated with pulmonary exacerbations. This study demonstrates that McKay agar can be used routinely to quantify the SMG from complex clinical samples.

Incidence, risk factors, and outcomes of Klebsiella pneumoniae bacteremia.

BACKGROUND: Although Klebsiella pneumoniae is the second most common cause of Gram-negative bloodstream infections, its epidemiology has not been defined in a nonselected population. We sought to describe the incidence of, risk factors for, and outcomes associated with K. pneumoniae bacteremia. METHODS: Population-based surveillance for K. pneumoniae bacteremia was conducted in the Calgary Health Region (population 1.2 million) from 2000 to 2007. RESULTS: A total of 640 episodes of K. pneumoniae bacteremia were identified for an overall annual population incidence of 7.1 per 100,000; 174 (27%) were nosocomial, 276 (43%) were healthcare-associated community onset, and 190 (30%) were community acquired. Elderly patients and men were at highest risk for K. pneumoniae bacteremia. Dialysis, solid-organ transplantation, chronic liver disease, and cancer were the most important risk factors for acquiring K. pneumoniae bacteremia. Rates of resistance to trimethoprim/sulfamethoxazole increased significantly during 2000 to 2007. The case fatality rate was 20%, and the annual population mortality rate was 1.3 per 100,000. Increasing age, nosocomial acquisition, non-urinary and non-biliary focus of infection, and several comorbid illnesses were independently associated with an increased risk of death. CONCLUSION: This is the first population-based study to document the major burden of illness associated with K. pneumoniae bacteremia and identifies groups at increased risk of acquiring and dying of these infections.

Staphylococcus aureus bloodstream infections: risk factors, outcomes, and the influence of methicillin resistance in Calgary, Canada, 2000-2006.

BACKGROUND: Reports have suggested that the epidemiological profile of invasive Staphylococcus aureus infections is changing. We sought to describe the epidemiological profile of S. aureus bacteremia and to assess whether the incidence and severity of and the antimicrobial resistance rates associated with this bacteremia are increasing. METHODS: Population-based surveillance for S. aureus bacteremias was conducted in the Calgary Health Region (population, 1.2 million) during 2000-2006. RESULTS: The annual incidence of S. aureus bacteremia was 19.7 cases/100,000 population. Although rates of health care-associated and nosocomial methicillin-susceptible S. aureus (MSSA) bacteremia were similar throughout the study, rates of community-acquired MSSA bacteremia gradually decreased, and rates of methicillin-resistant S. aureus (MRSA) bacteremia dramatically increased. The clonal type predominantly isolated was CMRSA-2 (i.e., Canadian [C] MRSA-2), but CMRSA-10 (USA300) strains have been increasingly isolated, especially from community-onset infections, since 2004. Dialysis dependence, organ transplantation, HIV infection, cancer, and diabetes were the most important risk factors and were comparable for MSSA and MRSA bacteremias. The overall case-fatality rate was higher among individuals with MRSA (39%) than among those with MSSA (24%; P< .0001). The annual overall population mortality rate associated with S. aureus bacteremia did not significantly change during the study. CONCLUSIONS: Although the overall influence of S. aureus bacteremia has not significantly changed, MRSA has emerged as an important etiology in our region.

Community-acquired lung abscess caused by Legionella micdadei in a myeloma patient receiving thalidomide treatment.

Legionella infection causes 2 to 14% of community-acquired pneumonia (CAP). Legionella micdadei constitutes <1% of these infections. We describe a case of cavitary L. micdadei CAP in a myeloma patient receiving thalidomide treatment. The importance of considering pneumonia and problems in diagnosing pneumonia caused by L. micdadei in this patient population are reviewed.

Invasive Candida species infections: a 5 year population-based assessment.

OBJECTIVES: Candida species have emerged as important causes of invasive infections and rates of resistance to standard antifungal therapies are rising. The objective of this study was to define the occurrence of, risk factors for, and antifungal susceptibilities of invasive Candida species infections in a large Canadian health region. METHODS: Population-based surveillance was conducted for invasive Candida species infections in the Calgary Health Region during a 5 year period and susceptibility testing was performed. RESULTS: The annual incidence of invasive Candida species infection was 2.9 per 100,000 population (0.2 and 2.8 per 100,000 for central nervous system and bloodstream infection, respectively). The very young and elderly were at highest risk for invasive Candida species infections. Several risk factors for developing invasive Candida species infection were identified with chronic haemodialysis, organ transplant recipient, and cancer patients at highest risk. Thirty percent (56/184; 43 susceptible, dose-dependent and 13 resistant) of isolates demonstrated reduced susceptibility to fluconazole. Only one (1%) isolate had reduced susceptibility to amphotericin B and six (3%) and three (2%) isolates had minimum inhibitory concentrations of >or=1 mg/L to voriconazole and caspofungin, respectively. Overall, 40% of patients died in-hospital for an annual mortality rate of 1.2 per 100,000. CONCLUSIONS: Candida species are an important cause of invasive infection and patients with co-morbidities and extremes of age are at highest risk. Alternatives to fluconazole should be considered for initial empiric therapy in patients with severe invasive Candida species infections.

Intensive care unit-acquired urinary tract infections in a regional critical care system.

INTRODUCTION: Few studies have evaluated urinary tract infections (UTIs) specifically acquired within intensive care units (ICUs), and the effect of such infections on patient outcome is unclear. The objectives of this study were to describe the occurrence, microbiology, and risk factors for acquiring UTIs in the ICU and to determine whether these infections independently increase mortality. METHODS: A surveillance cohort study was conducted among all adults admitted to multi-system and cardiovascular surgery ICUs in the Calgary Health Region (CHR, population about 1 million) between 1 January 2000 and 31 December 2002. RESULTS: During the 3 years, 4465 patients were admitted 4915 times to a CHR ICU for 48 hours or more. A total of 356 ICU-acquired UTIs (defined as at least 105 colony-forming units/ml of one or two organisms 48 hours or more after ICU admission) occurred among 290 (6.5%) patients, yielding an overall incidence density of ICU-acquired UTIs of 9.6 per 1000 ICU days. Four bacteremic/fungemic ICU-acquired UTIs occurred (0.1 per 1000 ICU days). Development of an ICU-acquired UTI was more common in women (relative risk [RR] 1.58; 95% confidence interval [CI] 1.43-1.75; P < 0.0001) and in medical (9%) compared with non-cardiac surgical (6%), and cardiac surgical patients (2%). The most common organisms isolated were Escherichia coli (23%), Candida albicans (20%), and Enterococcus species (15%). Antibiotic-resistant organisms were identified among 14% isolates. Although development of an ICU-acquired UTI was associated with significantly higher crude in-hospital mortality (86/290 [30%] vs. 862/4167 [21%]; RR = 1.43; 95% CI 1.19-1.73; P < 0.001); an ICU-acquired UTI was not an independent predictor for death. CONCLUSIONS: Development of an ICU-acquired UTI is common in critically ill patients. Although a marker of increased morbidity associated with critical illness, it is not a significant attributable cause of mortality.

Validation of a rapid diagnostic strategy for determination of significant bacterial counts in bronchoalveolar lavage samples.

CONTEXT: Bacterial cultures of bronchoscopic samples require 1 to 2 days for results to be available for use in clinical decisions. We developed a rapid diagnostic testing strategy that is highly sensitive for screening bacteria in bronchoalveolar lavage (BAL) samples, with results available within hours of collection. OBJECTIVE: To validate the ability of a bacterial adenosine triphosphate (ATP) assay and routine Gram stain microscopy to detect significant bacterial counts in BAL samples. DESIGN: Four hundred seventy-seven BAL samples from 319 patients suspected of having pneumonia were tested using a rapid diagnostic strategy, consisting of Gram stain and a bacterial ATP assay. Rapid results were compared with quantitative cultures with a positive cutoff of 10(4) CFU/mL or higher. RESULTS: Significant bacterial counts were identified in 107 samples (22%). The most common etiologic agents were Staphylococcus aureus (25%), Haemophilus influenzae (17%), and Streptococcus pneumoniae (12%). The rapid test results were false negative in 5 cases (S aureus in 2, both Klebsiella pneumoniae and S aureus in 1, and Stenotrophomonas maltophilia and S pneumoniae in 1 case each). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the rapid diagnostic strategy were 95.3%, 54.9%, 37.9%, 97.6%, and 63.9%, respectively. CONCLUSION: A negative result with this rapid diagnostic testing strategy rules out significant bacterial counts in BAL samples with a high degree of certainty and may allow use of narrow-spectrum antimicrobial agents or withholding of empiric antimicrobial therapy in patients suspected of having ventilator-associated pneumonia.

Population-based study of the epidemiology of and the risk factors for pyogenic liver abscess.

BACKGROUND & AIMS: Pyogenic liver abscess (PLA) is relatively uncommon in North America but is associated with significant morbidity and mortality. Our objective was to characterize the incidence of, risk factors for, and outcomes of PLA in a nonselected population. METHODS: Population-based surveillance was conducted in the Calgary Health Region (CHR) between April 1, 1999 and March 31, 2003. All adult CHR residents with PLA were identified, and charts were reviewed. RESULTS: Seventy-one CHR residents developed a PLA for an annual incidence of 2.3 per 100,000 population. There was an increasing incidence of PLA with advancing age. Men were at much higher risk of acquiring a PLA as compared to women (3.3 vs 1.3 per 100,000; relative risk [RR], 2.6; 95% confidence interval [CI], 1.5-4.6; P < .001), and this was observed across all age groups. A number of comorbid conditions were associated with significantly higher risk for developing a PLA including liver transplantation patients (RR, 444.8; 95% CI, 89.5-1356.0; P < .0001), diabetics (RR, 11.1; 95% CI, 6.3-19; P < .0001), and patients with a history of malignancy (RR, 13.3; 95% CI, 6.9-24.4; P < .0001). No other solid organ transplantation patient was at increased risk. All patients required admission to hospital (median length of stay, 16 days), and 7 (10%) patients died in hospital, corresponding to a mortality rate of 0.22 per 100,000 population. CONCLUSIONS: This study provides important data on the burden of PLA and identifies risk groups that might potentially benefit from preventive efforts.

Severe bloodstream infections: a population-based assessment.

OBJECTIVE: Although bloodstream infection commonly results in critical illness, population-based studies of the epidemiology of severe bloodstream infection are lacking. We sought to define the incidence and microbiology of severe bloodstream infection (bloodstream infection associated with intensive care unit admission within 48 hrs) and assess risk factors for acquisition and death. DESIGN: Population-based surveillance cohort. SETTING: Multidisciplinary and cardiovascular surgical intensive care units. PATIENTS: All adults with severe bloodstream infection in the Calgary Health Region (population approximately 1 million) during 2000-2002. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three hundred forty patients had 342 episodes of severe bloodstream infection (15.7 per 100,000 population/year). Several demographic and chronic conditions were significant risk factors for acquiring severe bloodstream infection (relative risk, 95% confidence interval) including age > or =65 yrs (7.0, 5.6-8.7), male gender (1.3, 1.1-1.6), urban residence (2.4, 1.2-5.6), hemodialysis (208.7, 142.9-296.3), diabetes mellitus (5.9, 4.4-7.8), alcoholism (5.6, 3.8-8.0), cancer (7.5, 5.3-10.3), and lung disease (3.8, 2.6-5.4). The most common etiologies were Staphylococcus aureus, Escherichia coli, and Streptococcus pneumoniae (3.0, 3.0, and 1.9 per 100,000/year, respectively). The case-fatality rate was 142 of 340 (42%) for an annual mortality rate of 6.5 per 100,000. Increased Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.1 per point; 95% confidence interval, 1.1-1.2) and presence of a comorbidity (odds ratio, 2.5; 95% confidence interval, 1.4-4.3) were significant independent predictors of death. CONCLUSIONS: Bloodstream infections are commonly severe enough to require management in an intensive care unit and are associated with a high mortality rate. Identification of risk factors for severe bloodstream infection may allow targeting of preventive efforts to individuals at greatest potential benefit.

Evaluation of a rapid bacterial ATP assay for screening BAL samples from ICU patients submitted for quantitative bacterial cultures.

A novel application of a rapid diagnostic technique for the detection of significant bacterial pathogens (>/=10(4) cfu/mL) in bronchoalveolar lavage (BAL) samples from critically ill ventilated patients is described. This rapid diagnostic assay (UTIscreen, Coral Biotechnology, San Diego, CA) utilizes a luciferin-luciferase reaction to detect bacterial adenosine triphosphate (ATP) and is currently commercially available for screening bacteriuria in urine specimens. One hundred and twenty-eight BAL samples were examined microscopically with Gram's stain and tested in parallel using the bacterial ATP assay and standard quantitative culture. The sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) for the detection of bacteria >/=10(4) cfu/ml in BAL specimens for the bacterial ATP assay was 87%, 59%, 39%, and 94%, and for the Gram's stain was 73%, 65%, 39%, and 89%, respectively. The diagnostic utility was improved by combining the results of Gram's stain/bacterial ATP assay results with Sn, Sp, PPV, and NPV of 97%, 38%, 32%, and 97% respectively. A combined negative rapid test consisting of Gram's stain/bacterial ATP assay rules out significant bacteria in BAL samples with a high degree of certainty. Future studies are needed to clinically validate these observations.