Harriet Hogevik

A clinical study of culture-negative endocarditis.

Culture-negative infective endocarditis (CNE) is a diagnostic problem in spite of improved echocardiographic and blood culturing techniques. We conducted the present study to estimate the proportion of CNE in patients with infective endocarditis, to investigate data regarding risk factors, and to evaluate the Duke and the modified Beth Israel criteria in patients with CNE.We evaluated 820 consecutive suspected episodes of infective endocarditis in adults at the Departments of Infectious Diseases in Göteborg and Borås, Sweden (1984–1996). All patients were diagnosed and treated according to a protocol; 487 episodes were identified as infective endocarditis. Episodes with absence of bacterial growth at blood culture were defined as CNE and were classified with the Duke and the modified Beth Israel criteria.We identified 116 CNE episodes (median age, 67 yr). Mortality was 7%, and in 15%, cardiac surgery was performed. The Duke criteria classified 20 definite, 80 possible, and 16 reject episodes. The modified Beth Israel criteria distinguished 13 definite, 15 probable, 27 possible, and 61 reject episodes. The proportion of CNE among patients with infective endocarditis varied from 19% to 27% at the 2 departments. Antibiotic treatment preceded blood culture in 45% of the CNE episodes.About 20% in a Scandinavian population of infective endocarditis patients have CNE. Antibiotic pretreatment explains less than 50% of all CNE episodes. The Duke criteria are more sensitive but less specific than the modified Beth Israel criteria in classifying patients with CNE.

Infective endocarditis : a diagnostic and therapeutic challenge for the new millennium

This review on infective endocarditis (IE) is based on clinical studies carried out in GöThis review on infective endocarditis (IE) is based on clinical studies carried out in Göteborg since 1984, data obtained from a Swedish national registry of IE since 1995 and existing literature. IE is still a great challenge in medicine, although improved bacteriological and echocardiographical techniques have facilitated diagnosis. In Sweden the incidence of IE is about 6 per 100,000 inhabitants a year. During recent decades IE has changed character. Patients are older, fever is often the only major symptom and a new murmur is less frequent. Streptococci, including viridans species and staphylococci, are still the most common bacteria found. Antibiotic treatment for 4-6 weeks may reduce mortality of IE to 30-50%. For further reduction, heart surgery is necessary in 20-25% of patients in order to remove infected tissues and restore valve function. Rapid diagnosis, careful antibiotic treatment and optimal surgery may reduce mortality associated with treatment to 10%. Antibiotic treatment is still mainly empiric. Penicillin and aminoglycoside for 2 weeks only seem to be effective in uncomplicated IE caused by alpha-streptococci. Otherwise, 4 weeks of treatment is needed, but aminoglycoside treatment may be reduced to 1 week in general and 2 weeks for enterococcal infections.

Fungal endocarditis — a report on seven cases and a brief review

SummaryCandida endocarditis is an unusual but severe complication of systemic infection caused byCandida albicans and occasionally by other fungal species. We describe seven cases that occurred during a period of 20 years in western Sweden. In four cases infections were located on prosthetic valves and in three cases native valves were involved. Three patients died of the disease in the acute phase. A definite diagnosis was established in one of four survivors. This patient had an aortic valve endocarditis and a saddle embolisation and was treated with immediate surgery, followed by intensive treatment with liposomal amphotericin B + flucytosine. Fungal endocarditis is still a serious disease with a high mortality and whenever the diagnosis is suspected, antifungal therapy must be started and transesophageal sonography should be performed to visualize vegetations. Immediate surgery should be considered.ZusammenfassungDieCandida-Endokarditis ist eine seltene, aber schwere Komplikation einer systemischen Infektion durchCandida albicans und gelegentlich auch durch andere Pilzspezies. Wir berichten über sieben Fälle, die in einem Zeitraum von 20 Jahren in Westschweden beobachtet wurden. In vier Fällen waren Klappenprothesen und in drei Fällen natürliche Klappen betroffen. Drei Patienten starben in der akuten Phase an der Krankheit. Bei einem der vier überlebenden Patienten konnte die Diagnose eindeutig gesichert werden. Dieser Patient hatte eine Aortenklappenendokarditis und einen reitenden Embolus. Er wurde sofort operiert und hochdosiert mit liposomalem Amphotericin B und mit Flucytosin behandelt. Die Pilzendokarditis ist nach wie vor eine ernste, mit hoher Letalität belastete Krankheit. Die antimykotische Therapie muß bereits beim ersten Verdacht begonnen werden. Um Vegetationen nachzuweisen, sollte die transösophageale Sonographie durchgeführt werden. Ein sofortiges chirurgisches Eingreifen ist zu erwägen.Candida endocarditis is an unusual but severe complication of systemic infection caused byCandida albicans and occasionally by other fungal species. We describe seven cases that occurred during a period of 20 years in western Sweden. In four cases infections were located on prosthetic valves and in three cases native valves were involved. Three patients died of the disease in the acute phase. A definite diagnosis was established in one of four survivors. This patient had an aortic valve endocarditis and a saddle embolisation and was treated with immediate surgery, followed by intensive treatment with liposomal amphotericin B + flucytosine. Fungal endocarditis is still a serious disease with a high mortality and whenever the diagnosis is suspected, antifungal therapy must be started and transesophageal sonography should be performed to visualize vegetations. Immediate surgery should be considered. DieCandida-Endokarditis ist eine seltene, aber schwere Komplikation einer systemischen Infektion durchCandida albicans und gelegentlich auch durch andere Pilzspezies. Wir berichten über sieben Fälle, die in einem Zeitraum von 20 Jahren in Westschweden beobachtet wurden. In vier Fällen waren Klappenprothesen und in drei Fällen natürliche Klappen betroffen. Drei Patienten starben in der akuten Phase an der Krankheit. Bei einem der vier überlebenden Patienten konnte die Diagnose eindeutig gesichert werden. Dieser Patient hatte eine Aortenklappenendokarditis und einen reitenden Embolus. Er wurde sofort operiert und hochdosiert mit liposomalem Amphotericin B und mit Flucytosin behandelt. Die Pilzendokarditis ist nach wie vor eine ernste, mit hoher Letalität belastete Krankheit. Die antimykotische Therapie muß bereits beim ersten Verdacht begonnen werden. Um Vegetationen nachzuweisen, sollte die transösophageale Sonographie durchgeführt werden. Ein sofortiges chirurgisches Eingreifen ist zu erwägen.

C-reactive protein is more sensitive than erythrocyte sedimentation rate for diagnosis of infective endocarditis

SummaryThe objective of this study was to evaluate the sensitivity of C-reactive protein (CRP) elevation compared to erythrocyte sedimentation rate (ESR), leucocyte count and thrombocyte count in the diagnosis of infective endocarditis (IE). It was designed as a prospective study of suspected episodes of IE in adults in tertiary care at a university-affiliated department of infectious diseases. In 89 episodes of IE, CRP was available from the start of treatment. Median age was 66 years, 45 were men and 44 women. Median CRP concentration was found to be 90 (range 0–357) mg/l with only 4% normal values. Episodes involving native valves had higher CRP than episodes occurring with prosthetic valves. Staphylococcal origin, short duration of symptoms, short duration of fever and highest recorded temperature all correlated to higher CRP levels. The CRP response was also prominent among patients >70 years old. Among non-responders, a few cases with simultaneous cirrhosis were noted. ESR was less sensitive than CRP, with a normal level in 28% of the episodes. It was concluded that CRP determination is superior to erythrocyte sedimentation rate, leucocyte count and thrombocyte count in the diagnosis of infective endocarditis.The objective of this study was to evaluate the sensitivity of C-reactive protein (CRP) elevation compared to erythrocyte sedimentation rate (ESR), leucocyte count and thrombocyte count in the diagnosis of infective endocarditis (IE). It was designed as a prospective study of suspected episodes of IE in adults in tertiary care at a university-affiliated department of infectious diseases. In 89 episodes of IE, CRP was available from the start of treatment. Median age was 66 years, 45 were men and 44 women. Median CRP concentration was found to be 90 (range 0–357) mg/l with only 4% normal values. Episodes involving native valves had higher CRP than episodes occurring with prosthetic valves. Staphylococcal origin, short duration of symptoms, short duration of fever and highest recorded temperature all correlated to higher CRP levels. The CRP response was also prominent among patients >70 years old. Among non-responders, a few cases with simultaneous cirrhosis were noted. ESR was less sensitive than CRP, with a normal level in 28% of the episodes. It was concluded that CRP determination is superior to erythrocyte sedimentation rate, leucocyte count and thrombocyte count in the diagnosis of infective endocarditis.

Comparative study of immune status to infectious agents in elderly patients with multiple myeloma, Waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance.

ABSTRACT Whereas patients with multiple myeloma (MM) have a well-documented susceptibility to infections, this has been less studied in other B-cell disorders, such as Waldenstroms macroglobulinemia (WM) and monoclonal gammopathy of undetermined significance (MGUS). We investigated the humoral immunity to 24 different pathogens in elderly patients with MM (n = 25), WM (n = 16), and MGUS (n = 18) and in age-matched controls (n = 20). Antibody titers against pneumococci, staphylococcal alpha-toxin, tetanus and diphtheria toxoids, and varicella, mumps, and rubella viruses were most depressed in MM patients, next to lowest in WM and MGUS patients, and highest in the controls. In contrast, levels of antibodies specific for staphylococcal teichoic acid, Moraxella catarrhalis, candida, aspergillus, and measles virus were similarly decreased in MM and MGUS patients. Comparable titers in all study groups were seen against Haemophilus influenzae type b (Hib), borrelia, toxoplasma, and members of the herpesvirus family. Finally, a uniform lack of antibodies was noted against Streptococcus pyogenes, salmonella, yersinia, brucella, francisella, and herpes simplex virus type 2. To conclude, although MM patients displayed the most depressed humoral immunity, significantly decreased antibody levels were also evident in patients with WM and MGUS, particularly against Staphylococcus aureus, pneumococci, and varicella. Conversely, immunity was retained for Hib and certain herpesviruses in all study groups.

Bartonella and Coxiella Antibodies in 334 Prospectively Studied Episodes of Infective Endocarditis in Sweden

Bartonella spp. have been identified as aetiological agents in culture-negative infective endocarditis (IE). Coxiella burnetii may cause chronic Q-fever with endocarditis. 334 blood samples collected from 329 patients (334 episodes) with IE diagnosed between 1984 and 1996 in Göteborg, Sweden, were investigated for antibodies to Bartonella spp. and C. burnetii. 71 of the episodes (21%) were blood culture negative. A microimmunofluorescence assay revealed immunoglobulin G (IgG) antibodies to Bartonella in 13 of the culture verified episodes and in 2 of the culture-negative episodes. Three of the patients had IgG antibodies to ≥ 200 in the blood culture-verified group, but none had a titre ≥ 800, the cut-off level for Bartonella endocarditis. One patient had elevated antibodies to C. burnetii, diagnosing chronic Q-fever endocarditis. In conclusion, serologically verified Bartonella endocarditis is not prevalent in western Sweden and Q-fever endocarditis is rare.

A 10-year survey of blood culture negative endocarditis in Sweden: Aminoglycoside therapy is important for survival

We estimated the prevalence of blood culture negative endocarditis (CNE) and described and analysed data with special attention to antibiotic treatment from patients with infective endocarditis (IE) reported to the Swedish endocarditis registry during the 10-y period 1995–2004. All 29 departments of infectious diseases in Sweden reported data to the registry. During the 10-y period, 2509 IE episodes (78% Duke definite) were identified in 2410 patients. 304 CNE episodes (25% Duke definite) were found. The proportion of CNE was measured to be 12% of all IE episodes. Fatal outcome occurred in 10.7% of all IE patients and in 5% of the CNE patients. The risk of dying was significantly increased in female (9%) compared to male (2%) CNE patients (OR 5.1). Mortality was significantly decreased in patients treated with an aminoglycoside (3%) versus patients without aminoglycoside therapy (13%), OR 0.2. In conclusion, the prevalence of CNE was 12% in Swedish IE patients in a 10-y survey. The mortality in IE was low (10.7%) and 4.6% for CNE. Women have higher mortality rates than men in CNE. CNE patients who received aminoglycoside therapy survived more frequently than CNE patients without this therapy.

Poor Correlation between Pneumococcal IgG and IgM Titers and Opsonophagocytic Activity in Vaccinated Patients with Multiple Myeloma and Waldenstrom's Macroglobulinemia

ABSTRACT Patients with multiple myeloma and other B cell disorders respond poorly to pneumococcal vaccination. Vaccine responsiveness is commonly determined by measuring pneumococcal serotype-specific antibodies by enzyme-linked immunosorbent assay (ELISA), by a functional opsonophagocytosis assay (OPA), or by both assays. We compared the two methods in vaccinated elderly patients with multiple myeloma, Waldenstroms macroglobulinemia, and monoclonal gammopathy of undetermined significance (MGUS). Postvaccination sera from 45 patients (n = 15 from each patient group) and 15 control subjects were analyzed by multiplexed OPA for pneumococcal serotypes 4, 6B, 14, and 23F, and the results were compared to IgG and IgM antibody titers measured by ELISA. While there were significant correlations between pneumococcal OPA and IgG titers for all serotypes among the control subjects (correlation coefficients [r] between 0.51 and 0.85), no significant correlations were seen for any of the investigated serotypes in the myeloma group (r = −0.18 to 0.21) or in the group with Waldenstroms macroglobulinemia (borderline significant correlations for 2 of 4 serotypes). The MGUS group resembled the control group by having good agreement between the two test methods for 3 of 4 serotypes (r = 0.53 to 0.80). Pneumococcal postvaccination IgM titers were very low in the myeloma patients compared to the other groups and did not correlate with the OPA results. To summarize, our data indicate that ELISA measurements may overestimate antipneumococcal immunity in elderly subjects with B cell malignancies and that a functional antibody test should be used specifically for myeloma and Waldenstroms macroglobulinemia patients.

Comments on: Swedish guidelines for diagnosis and treatment of infective endocarditis recommend overuse of transoesophageal echocardiography

First, we appreciate your interest in the Swedish guidelines for infective endocarditis (IE) [1]. IE is a severe infection with a mortality rate of 20% in most series. The prognosis has improved during recent decades due to the introduction of echocardiography and surgery in the acute phase. IE is treated with parenteral antibiotics during hospitalization for 2 6 weeks. Acute surgery is performed in about 25% of surgery of all cases. If not diagnosed and thus not treated, IE is a universally fatal disease. Also a substantial proportion of cured patients might suffer from cardiac or cerebral permanent sequelae if treatment is delayed. Echocardiography has vastly improved the possibility to diagnose infective endocarditis and the findings constitute major criteria for the diagnosis [2,3]. Echocardiography can identify vegetations, abscesses and heart failure but it should also be stressed that a negative finding can significantly reduce but not rule out a suspicion of IE. However, we do not agree with you that the guidelines recommend an overuse of transoesophageal echocardiography (TEE). To our knowledge, there are few studies to compare transthoracic echocardiography (TTE) and TEE in recent y. Two of them are mentioned in the guidelines [4,5], and a third by Jassal et al. [6] was published after the guidelines were finally sent to the journal for publication. In the last paper [6], 36 patients at intermediate risk for infective endocarditis were evaluated: in 3/19 patients vegetations were identified by TEE that was not identified by TTE, and TEE was also needed to exclude infective endocarditis in another 2 patients. We are aware that the TTE technique has been improved in recent y. We look forward to further studies in the future. ‘Overuse of TEE’ was discussed in a publication by Thangaroopan et al. [7]. The problem is caused mainly when one performs TEE in patients with low pretest likelihood for IE. False positive findings might outnumber the diagnosis of a few additional true IE cases [7]. An ‘overuse of TEE’ may be due to physicians sending patients to TEE having a lack of knowledge about the disease infective endocarditis. We definitely agree with you that the guidelines should indicate that a new TEE should be performed if the first is negative, if infective endocarditis is still suspected. The guidelines will be revised at the end of this y and we will discuss this topic again; perhaps an algorithm could be useful, mainly for cases with a low suspicion of infective endocarditis. Until further studies are performed, we still recommend TEE when there are patients with a strong suspicion of infective endocarditis and it is mandatory when suspecting prosthetic valve endocarditis, pacemaker endocarditis or Staphylococcus