Anders Thalme

Prospective Study of Prognostic Factors in Community-Acquired Bacteremic Pneumococcal Disease in 5 Countries

To define the influence of prognostic factors in patients with community-acquired pneumococcal bacteremia, a 2-year prospective study was performed in 5 centers in Canada, the United States, the United Kingdom, Spain, and Sweden. By multivariate analysis, the independent predictors of death among the 460 patients were age >65 years (odds ratio [OR], 2.2), living in a nursing home (OR, 2.8), presence of chronic pulmonary disease (OR, 2.5), high acute physiology score (OR for scores 9-14, 7.6; for scores 15-17, 22; and for scores >17, 41), and need for mechanical ventilation (OR, 4.4). Of patients with meningitis, 26% died. Of patients with pneumonia without meningitis, 19% of those with >/=2 lobes and 7% of those with only 1 lobe involved (P=.0016) died. The case-fatality rate differed significantly among the centers: 20% in the United States and Spain, 13% in the United Kingdom, 8% in Sweden, and 6% in Canada. Differences of disease severity and of frequencies and impact of underlying chronic conditions were factors of probable importance for different outcomes.

Swedish guidelines for diagnosis and treatment of infective endocarditis

Swedish guidelines for diagnosis and treatment of infective endocarditis (IE) by consensus of experts are based on clinical experience and reports from the literature. Recommendations are evidence based. For diagnosis 3 blood cultures should be drawn; chest X-ray, electrocardiogram, and echocardiography preferably transoesophageal should be carried out. Blood cultures should be kept for 5 d and precede intravenous antibiotic therapy. In patients with native valves and suspicion of staphylococcal aetiology, cloxacillin and gentamicin should be given as empirical treatment. If non-staphylococcal etiology is most probable, penicillin G and gentamicin treatment should be started. In patients with prosthetic valves treatment with vancomycin, gentamicin and rifampicin is recommended. Patients with blood culture negative IE are recommended penicillin G (changed to cefuroxime in treatment failure) and gentamicin for native valve IE and vancomycin, gentamicin and rifampicin for prosthetic valve IE, respectively. Isolates of viridans group streptococci and enterococci should be subtyped and MIC should be determined for penicillin G and aminoglycosides. Antibiotic treatment should be chosen according to sensitivity pattern given 2–6 weeks intravenously. Cardiac valve surgery should be considered early, especially in patients with left-sided IE and/or prosthetic heart valves. Absolute indications for surgery are severe heart failure, paravalvular abscess, lack of response to antibiotic therapy, unstable prosthesis and multiple embolies. Follow-up echocardiography should be performed on clinical indications.

In-hospital and long-term mortality in infective endocarditis in injecting drug users compared to non-drug users: A retrospective study of 192 episodes

In a retrospective study, in-hospital and long-term mortality for patients with infective endocarditis (IE) was analysed. The study was conducted at a department of infectious diseases in Stockholm, Sweden. Mortality was compared between injecting drug users (IDUs) and patients without drug abuse (non-IDUs). 192 episodes of IE from 1995 to 2000 were analysed, 60 in IDUs and 135 in non-IDUs, median follow-up 4.4 y. Episodes were classified using the Duke criteria: 145 definite and 47 possible. Of 53 definite episodes in IDUs, 55% were right-sided IE and 43% left-sided IE (including combined left- and right-sided). Surgical treatment was used in 34/145 definite episodes, all being left-sided IE. The in-hospital mortality was 14/145 (9.6%). There was no difference in in-hospital mortality between patient groups with left-sided IE. The IDU patients with left-sided IE had a higher long-term mortality with the increased mortality rate explained by late deaths in the surgically treated IDUs. Treatment results for IDUs with right-sided IE were good with no in-hospital mortality, no relapses and no increase in long-term mortality. This difference in prognosis between left-sided and right-sided IE in IDUs makes high quality echocardiography important to identify patients with left-sided IE and worse prognosis.

Candida albicans tricuspid valve endocarditis in an intravenous drug addict: Successful treatment with fluconazole

An addicted, intravenous drug user was treated for Candida albicans tricuspid valve endocarditis with high dose fluconazole for 8 months, without relapse after 30 months.

Streptococcus viridans septicaemia: a comparison study in patients admitted to the departments of infectious diseases and haematology in a university hospital.

Infective endocarditis caused by viridans streptococci is a well-described disease. Streptococcus viridans is also an important etiologic agent causing septicaemia in neutropenic patients with haematological diseases. In this study we retrospectively reviewed charts from 111 patients with 121 episodes of viridans streptococci septicaemia during the period 1992-97 for clinical data, presence of endocarditis, subtype and outcome. Forty-seven episodes of S. viridans septicaemia were documented in 45 non-neutropenic patients treated at the Department of Infectious Diseases (Group A). Thirty of these episodes were defined as definite and 9 as possible infective endocarditis, using Dukes critera. Seventy-four episodes of S. viridans septicaemia were identified in 66 patients treated at the Department of Haematology (Group B), only 1 of which fulfilled the criteria for possible infective endocarditis. S. sanguis was the most common subtype (18/47; 38%) in Group A and S. mitis was the major subtype (51/74; 69%) in Group B.

Incidence and outcome of Staphylococcus aureus endocarditis—a 10-year single-centre northern European experience

Staphylococcus aureus is a leading cause of infective endocarditis. Little has been published on the outcome and epidemiology of S. aureus endocarditis (SAE) in the twenty-first century. Our aim was to evaluate the short-term and long-term outcome of SAE in Stockholm, Sweden, and assess its incidence over time. Patients treated for SAE from January 2004 through December 2013 were retrospectively identified at the Karolinska University Hospital. Clinical data were obtained from medical records and the diagnosis was verified according to the modified Duke criteria. Of 245 SAE cases, 152 (62%) were left-sided and 120 (49%) occurred in intravenous drug users. The calculated incidence in Stockholm County was 1.56/100 000 person-years, increasing from 1.28 in 2004-08 to 1.82/100 000 person-years in 2009-13 (p 0.002). In-hospital and 1-year mortality rates were 9.0% (22/245) and 19.5% (46/236), respectively. Age (OR 1.06 per year) and female sex (OR 3.0) were independently associated with in-hospital mortality in multivariate analysis. Involvement of the central nervous system (CNS) was observed in 30 (12%) patients, and valvular surgery was performed during hospitalization in 37 (15%). In left-sided endocarditis the strongest predictors for surgery were severe valvular insufficiency (OR 8.9), lower age (OR 1.07 per year) and no intravenous drug use (OR 10.7), and for CNS involvement lower age (OR 1.04 per year). In conclusion we noted low mortality, low CNS complication rate, and low valvular surgery frequency associated with SAE in our setting. The incidence was high and increased over time. The study provides an update on the outcome and epidemiology of SAE in the twenty-first century.

Staphylococcus aureus bacteraemia and endocarditis – epidemiology and outcome: a review

Abstract Purpose: To review the epidemiology of Staphylococcus aureus bacteraemia (SAB) and endocarditis (SAE), and discuss the short- and long-term outcome.  Materials and methods: A literature review of the epidemiology of SAB and SAE. Results: The reported incidence of SAB in Western countries is 16–41/100,000 person-years. Increasing incidence has been observed in many regions, in Iceland by 27% during 1995–2008. The increase is believed to depend on changes in population risk factors and possibly better and more frequent utilization of diagnostic procedures. S. aureus is now the leading causes of infective endocarditis (IE) in many regions of the world. It accounts for 15–40% of all IE cases, and the majority of cases in people who inject drugs (PWID). Recently, the incidence of SAE in PWID in Stockholm, Sweden, was found to be 2.5/1000 person-years, with an in-hospital mortality of 2.5% in PWID as compared to 15% in non-drug users. The 30-day mortality associated with SAB amounts to 15–25% among adults in Western countries, but is lower in children (0–9%). Mortality associated with SAE is high (generally 20–30% in-hospital mortality), and symptomatic cerebral embolizations are common (12–35%). The 1-year mortality reported after SAB and SAE is 19–62% and reflects deaths from underlying diseases and complications caused by the infection. In a subset of SAE cases, valvular heart surgery is needed (15–45%), but active intravenous drug use seems to be a reason to refrain from surgery. Despite its importance, there are insufficient data on the optimal management of SAB and SAE, especially on the required duration of antibiotic therapy.  Conclusions: The epidemiology of SAB and SAE has been changing in the past decades. They still carry a substantial morbidity and mortality. Intensified studies on treatment are warranted for improving patient outcome.

Low mortality but increasing incidence of Staphylococcus aureus endocarditis in people who inject drugs: Experience from a Swedish referral hospital

Abstract Staphylococcus aureus is a leading cause of infective endocarditis in people who inject drugs (PWID). The management of S aureus endocarditis (SAE) in PWID can be problematic. The objective of this retrospective observational study was to assess the epidemiology, clinical characteristics, and mortality of S aureus endocarditis (SAE) in PWID in Stockholm, Sweden. The Department of Infectious Diseases at the Karolinska University Hospital serves as a regional referral center for drug users with severe infections. Patients with active intravenous drug use treated for SAE at the department between January 2004 and December 2013 were retrospectively identified. Clinical and microbiological data were obtained from medical records and the diagnosis verified according to the modified Duke criteria. In total, 120 SAE episodes related to intravenous drug use were identified. Its incidence in Stockholm was 0.76/100,000 adult person-years for the entire period, increasing from 0.52/100,000 person-years in 2004 to 2008 to 0.99 in 2009 to 2013 (P = 0.02). The SAE incidence among PWID specifically was 249 (range 153–649) /100,000 person-years. Forty-two (35%) episodes were left-sided, and multiple valves were involved in 26 (22%). Cardiac valve surgery was performed in 10 (8%) episodes, all left-sided. The in-hospital and 1-year mortality rates were 2.5% (3 deaths) and 8.0% (9 deaths), respectively. We noted a high and increasing incidence over time of SAE related to intravenous drug use in Stockholm. The increased incidence partly reflects a rising number of PWID during the study period. The low mortality noted, despite a substantial proportion with left-sided endocarditis, probably in part reflects the quality of care obtained at a large and specialized referral center for drug users with severe infections.

Dynamics of Two Separate but Linked HIV-1 CRF01_AE Outbreaks among Injection Drug Users in Stockholm, Sweden, and Helsinki, Finland

ABSTRACT Detailed phylogenetic analyses were performed to characterize an HIV-1 outbreak among injection drug users (IDUs) in Stockholm, Sweden, in 2006. This study investigated the source and dynamics of HIV-1 spread during the outbreak as well as associated demographic and clinical factors. Seventy Swedish IDUs diagnosed during 2004 to 2007 were studied. Demographic, clinical, and laboratory data were collected, and the V3 region of the HIV-1 envelope gene was sequenced to allow detailed phylogenetic analyses. The results showed that the Stockholm outbreak was caused by a CRF01_AE variant imported from Helsinki, Finland, around 2003, which was quiescent until the outbreak started in 2006. Local Swedish subtype B variants continued to spread at a lower rate. The number of new CRF01_AE cases over a rooted phylogenetic tree accurately reflected the transmission dynamics and showed a temporary increase, by a factor of 12, in HIV incidence during the outbreak. Virus levels were similar in CRF01_AE and subtype B infections, arguing against differences in contagiousness. Similarly, there were no major differences in other baseline characteristics. Instead, the outbreak in Stockholm (and Helsinki) was best explained by an introduction of HIV into a standing network of previously uninfected IDUs. The combination of phylogenetics and epidemiological data creates a powerful tool for investigating outbreaks of HIV and other infectious diseases that could improve surveillance and prevention.

The dynamics of two separate but linked CRF01_AE outbreaks among IDUs in Stockholm and Helsinki

ABSTRACT Detailed phylogenetic analyses were performed to characterize an HIV-1 outbreak among injection drug users (IDUs) in Stockholm, Sweden, in 2006. This study investigated the source and dynamics of HIV-1 spread during the outbreak as well as associated demographic and clinical factors. Seventy Swedish IDUs diagnosed during 2004 to 2007 were studied. Demographic, clinical, and laboratory data were collected, and the V3 region of the HIV-1 envelope gene was sequenced to allow detailed phylogenetic analyses. The results showed that the Stockholm outbreak was caused by a CRF01_AE variant imported from Helsinki, Finland, around 2003, which was quiescent until the outbreak started in 2006. Local Swedish subtype B variants continued to spread at a lower rate. The number of new CRF01_AE cases over a rooted phylogenetic tree accurately reflected the transmission dynamics and showed a temporary increase, by a factor of 12, in HIV incidence during the outbreak. Virus levels were similar in CRF01_AE and subtype B infections, arguing against differences in contagiousness. Similarly, there were no major differences in other baseline characteristics. Instead, the outbreak in Stockholm (and Helsinki) was best explained by an introduction of HIV into a standing network of previously uninfected IDUs. The combination of phylogenetics and epidemiological data creates a powerful tool for investigating outbreaks of HIV and other infectious diseases that could improve surveillance and prevention.