Abstract 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.
Abstract Purpose To determine the rate of Staphylococcus aureus nasal colonization at admission to intensive care units (ICU) and assess its effect on the development of an ICU-acquired S aureus ...infection. Materials and Methods We screened all ICU admissions for nasal colonization within the Calgary Health Region from October 2005 to September 2006 and followed up patients to hospital discharge or death or S aureus infection to 30 days. Results One thousand three hundred eight patients were admitted to ICU for more than 48 hours and screened for nasal colonization. Fifty (4%) were methicillin-resistant S aureus (MRSA)–positive, 311 (24%) were methicillin-sensitive S aureus (MSSA)–positive, and 947 (72%) were nasal screen–negative. Overall, 5% (63/1239) of patients uninfected at ICU admission developed an ICU-acquired S aureus infection. The rate of ICU-acquired infection was 5% in MRSA colonized patients, 12% in MSSA colonized patients, and 3% in noncolonized patients. A positive nasal screen (odds ratio OR, 4.7; 95% confidence interval CI 2.7-7.9), neuro/trauma patients (OR, 3.1; 95% CI, 1.8-5.2), and higher first Therapeutic Intervention Scoring System score (OR, 1.03 per point; 95% CI, 1.01-1.05) were independent predictors for developing an ICU-acquired S aureus infection. Conclusions Nasal colonization with S aureus is a significant risk factor for ICU-acquired S aureus infections, and strategies to control these infections should target both MSSA and MRSA colonization.
Summary 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.
The reluctance to use organs from donors who have died from severe infections is based on the potential transmission of an infectious agent to the recipient and on the uncertainty about allograft ...function in the setting of severe donor sepsis.
From 1999 to 2007, donor hospital records were reviewed which focused on microbiology cultures and sensitivity results; type and duration of antimicrobial therapy; hemodynamic data, results of echocardiogram, and imaging studies. Preliminary positive and negative results from pre-harvest blood, respiratory, urine, and cerebrospinal fluid cultures were verified with the procurement agency. The harvesting surgeon performed gross inspection of donor valvular structures.
Nine donor hearts were transplanted from patients who expired from community onset infections with severe septic shock, meningitis, and/or pneumonia caused by Streptococcus pneumoniae (n = 4), Streptococcus milleri (n = 2), Neisseria meningitidis (n = 2), and unidentified gram- positive cocci (n = 1). Four donors had probable infection-induced intracranial hemorrhage, and all donors were vasopressor-dependent before organ procurement. No evidence of donor-transmitted infection, sepsis, or rejection was observed, and long-term function remained excellent; allograft dysfunction in three patients resolved after transplant. Our series of nine donors represents approximately 1.3% of successfully transplanted cardiac allografts during the respective period of review.
Patients succumbing to severe infections (meningitis, pneumonia, and septic shock) should not be arbitrarily excluded for possible heart donation. Assessing the suitability of donors with severe infections requires flawless communication between the donor and transplant facility, including a comprehensive evaluation of donor infection and pathogen(s), severity of sepsis, adequacy of antimicrobial treatment, and the degree of sepsis-induced myocardial dysfunction.
Summary Background Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by ...thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage. Methods MISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany. We used a computer-generated allocation sequence with a block size of four to centrally randomise patients aged 18–80 years with a non-traumatic (spontaneous) intracerebral haemorrhage of 20 mL or higher to standard medical care or image-guided MIS plus alteplase (0·3 mg or 1·0 mg every 8 h for up to nine doses) to remove clots using surgical aspiration followed by alteplase clot irrigation. Primary outcomes were all safety outcomes: 30 day mortality, 7 day procedure-related mortality, 72 h symptomatic bleeding, and 30 day brain infections. This trial is registered with ClinicalTrials.gov , number NCT00224770. Findings Between Feb 2, 2006, and April 8, 2013, 96 patients were randomly allocated and completed follow-up: 54 (56%) in the MIS plus alteplase group and 42 (44%) in the standard medical care group. The primary outcomes did not differ between the standard medical care and MIS plus alteplase groups: 30 day mortality (four 9·5%, 95% CI 2·7–22.6 vs eight 14·8%, 6·6–27·1, p=0·542), 7 day mortality (zero 0%, 0–8·4 vs one 1·9%, 0·1–9·9, p=0·562), symptomatic bleeding (one 2·4%, 0·1–12·6 vs five 9·3%, 3·1–20·3, p=0·226), and brain bacterial infections (one 2·4%, 0·1–12·6 vs zero 0%, 0–6·6, p=0·438). Asymptomatic haemorrhages were more common in the MIS plus alteplase group than in the standard medical care group (12 22·2%; 95% CI 12·0–35·6 vs three 7·1%; 1·5–19·5; p=0·051). Interpretation MIS plus alteplase seems to be safe in patients with intracerebral haemorrhage, but increased asymptomatic bleeding is a major cautionary finding. These results, if replicable, could lead to the addition of surgical management as a therapeutic strategy for intracerebral haemorrhage. Funding National Institute of Neurological Disorders and Stroke, Genentech, and Codman.
Summary Background The emergence and spread of high levels of HIV-1 drug resistance in resource-limited settings where combination antiretroviral treatment has been scaled up could compromise the ...effectiveness of national HIV treatment programmes. We aimed to estimate changes in the prevalence of HIV-1 drug resistance in treatment-naive individuals with HIV since initiation of rollout in resource-limited settings. Methods We did a systematic search for studies and conference abstracts published between January, 2001, and July, 2011, and included additional data from the WHO HIV drug resistance surveillance programme. We assessed the prevalence of drug-resistance mutations in untreated individuals with respect to time since rollout in a series of random-effects meta-regression models. Findings Study-level data were available for 26 102 patients from sub-Saharan Africa, Asia, and Latin America. We recorded no difference between chronic and recent infection on the prevalence of one or more drug-resistance mutations for any region. East Africa had the highest estimated rate of increase at 29% per year (95% CI 15 to 45; p=0·0001) since rollout, with an estimated prevalence of HIV-1 drug resistance at 8 years after rollout of 7·4% (4·3 to 12·7). We recorded an annual increase of 14% (0% to 29%; p=0·054) in southern Africa and a non-significant increase of 3% (–0·9 to 16; p=0·618) in west and central Africa. There was no change in resistance over time in Latin America, and because of much country-level heterogeneity the meta-regression analysis was not appropriate for Asia. With respect to class of antiretroviral, there were substantial increases in resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) in east Africa (36% per year 21 to 52; p<0·0001) and southern Africa (23% per year 7 to 42; p=0·0049). No increase was noted for the other drug classes in any region. Interpretation Our findings suggest a significant increase in prevalence of drug resistance over time since antiretroviral rollout in regions of sub-Saharan Africa; this rise is driven by NNRTI resistance in studies from east and southern Africa. The findings are of concern and draw attention to the need for enhanced surveillance and drug-resistance prevention efforts by national HIV treatment programmes. Nevertheless, estimated levels, although increasing, are not unexpected in view of the large expansion of antiretroviral treatment coverage seen in low-income and middle-income countries—no changes in antiretroviral treatment guidelines are warranted at the moment. Funding Bill & Melinda Gates Foundation and the European Community's Seventh Framework Programme
Summary Background Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove ...intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov , NCT00784134. Findings Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio RR 1·06 95% CI 0·88–1·28; p=0·554). A difference of 3·5% (RR 1·08 95% CI 0·90–1·29, p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 18% vs saline 73 29%, hazard ratio 0·60 95% CI 0·41–0·86, p=0·006), but a greater proportion with mRS 5 (42 17% vs 21 9%; RR 1·99 95% CI 1·22–3·26, p=0·007). Ventriculitis (17 7% alteplase vs 31 12% saline; RR 0·55 95% CI 0·31–0·97, p=0·048) and serious adverse events (114 46% alteplase vs 151 60% saline; RR 0·76 95% CI 0·64–0·90, p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six 2% in the alteplase group vs five 2% in the saline group; RR 1·21 95% CI 0·37–3·91, p=0·771) was similar. Interpretation In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status. Funding National Institute of Neurological Disorders and Stroke.
Background. A study was conducted in the Calgary Health Region between May 2002 and April 2004 to define the population‐based epidemiological characteristics of infections caused by ...imipenem‐resistant Pseudomonas aeruginosa and to explore the clinical outcomes due to metallo‐β‐lactamase (MBL)–producing and non–MBL‐producing strains. Methods. Detailed clinical information was obtained by chart review, and phenotypic and molecular characterizations were performed using the MBL E‐test, polymerase chain reaction with sequencing, and pulsed‐field gel electrophoresis. Results. A total of 228 patients with infections caused by imipenem‐resistant P. aeruginosa were identified (annual incidence, 10.5 cases/100,000 population), with the highest incidence rate in those ⩾75 years old. MBL‐producing strains (98/228) were associated with higher rates of multidrug resistance and bacteremia. Ninety MBL‐producing strains also produced VIM‐2, 4 produced IMP‐7, and 4 were unclassified. A cluster of VIM‐2–producing strains was responsible for a nosocomial outbreak during 2003. The case‐fatality rate was significantly higher for infections caused by MBL‐producing strains than for those caused by non–MBL‐producing strains (25% vs. 13%; relative risk, 1.98 95% confidence interval, 1.00–3.90; P=.05). Conclusion. MBL‐producing P. aeruginosa strains were associated with a higher case‐fatality rate and invasive disease. Our study highlights the potential importance of molecular laboratory techniques in infection control and patient care.
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